|Year : 2015 | Volume
| Issue : 1 | Page : 38-51
Prostanoids and parasitic diseases
Amany M Eida MD
Department of Parasitology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt
|Date of Submission||10-Dec-2014|
|Date of Acceptance||18-May-2015|
|Date of Web Publication||24-Aug-2015|
Amany M Eida
Department of Parasitology, Faculty of Medicine, Suez Canal University, 41522, Ismailia
Source of Support: None, Conflict of Interest: None
The eicosanoid family includes prostanoids, leukotrienes, and other oxygenated derivatives. Prostanoids are a major class of the eicosanoid family derived from metabolism of arachidonic acid by the action of cyclooxygenase enzymes (COX). They are further subdivided into three main groups: prostaglandins (PGs), thromboxanes (TXs), and prostacyclins. PGs were first discovered as uterotonic substances in human seminal ﬂuid in 1930. In the late 1950s to mid-1960s, their structures were studied and identified as being derived from unsaturated fatty acids. Prostanoids are produced by many cell types such as vascular endothelium, leukocytes, and the pathogens themselves. Prostanoid production is controlled by expression of different enzymes engaged in prostanoid biosynthesis, and by the distribution of different specific prostanoid synthases within those cells that determine their effect on the immune system. The production of prostanoids differs from one cell type to another; for example, dendritic cells predominately produce PG E 2 (PGE 2 ) and TXA 2 , whereas mastocytes produce PGD 2 . All inflammatory cells, including monocytes/macrophages, and neutrophils, are the main source of COX metabolites.
Produced in response to various physiological and pathological stimuli, PGs are noted as key participants in autoimmune immunopathology, infectious diseases, and cancer. Other reports have shown that PGIs are formed by endothelial and smooth muscle cells, and TXAs are formed by platelets and lungs; PGI 2 and some other PGs are produced by interactions between cells using enzymes in adjacent cells; for example, platelet-produced PGH 2 is converted to PGI 2 in the vascular epithelium.
PGs secreted in the saliva of blood-sucking arthropods increase local blood flow and maintain the supply for feeding; they were also reported to increase immune suppression, allowing prolongation of attachment by ticks. Progressive studies demonstrated that, besides insects, pathogenic fungi, protozoa, and parasitic worms produce PGs.
This review focuses on induced efforts to study prostanoids and their relation to different parasitic diseases.
AA: Arachidonic acid; COXs: Cyclooxygenase enzymes; CyPG: Cyclopentanone; DC: Dendritic cell; GST: Glutathione-S-transferase; GA: Glycyrrhizic acid; MAP: Mitogen-activated protein; MIF: Macrophage migration inhibitory factor; NO: Nitric oxide; PBMC: Peripheral blood mononuclear cells; PG: Prostaglandin; PG12: Prostacyclin; PGE2: Prostaglandin E2; PL: Phospholipase; PPAR: Peroxisome proliferator-activated receptors; TGF: Transforming growth factor; TNF: Tumor necrosis factor; TP: Thromboxan receptor; TX: Thromboxane.
Keywords: anti-inflammatory drugs, dendritic cells, helminthes, immunomodulation, prostanoid receptors, prostanoids, protozoa
|How to cite this article:|
Eida AM. Prostanoids and parasitic diseases. Parasitol United J 2015;8:38-51
| Prostanoid synthesis|| |
Arachidonic acid (AA) is a 20-carbon polyunsaturated fatty acid. It is derived from linoleic acid and becomes stored as part of glycerophospholipids in the lipid bilayer of the plasma membrane ,,,,,,,,,,,,, . Released by the action of phospholipase (PL), AA is metabolized by independent metabolic pathways and the COX pathway producing prostaglandins (PGs) and thromboxane A 2 (TXA 2 )  . It is hydrolyzed by COX enzymes to PGH 2  . In humans, there are two COX isoenzymes (COX-1 and COX-2) , . Through two sequential reactions the COX isoforms generate PGH 2 , which is the central substrate for synthesis of all PGs and TXA 2 ,, . PGH 2 is the common substrate for a series of cell-specific terminal PG synthases that produce PGD 2 , PGE 2 , PGF 2α, PGI 2 , and TXA 2  ([Figure 1]).
|Figure 1 Pathways of prostanoid biosynthesis .|
PPAR, peroxisome proliferator-activated r eceptor.
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| Biological functions of prostanoids|| |
TX and prostacyclin (PGI 2 ) regulate platelet aggregation, where the former induces coagulation and vasoconstriction and the latter is a vasodilator and anticoagulant  . It was shown that products of COX metabolites act as anti-inflammatory lipid mediators during resolution of infection and at later stage of inflammation  . While PG and PGI 2 proinﬂammatory functions are well documented  , prostanoids participate in tissue fibrosis and mucus secretion , , vascular tone, inflammation, ischemia, and tissue homeostasis  . Prostanoids also regulate capillary bed perfusion, vascular endothelium permeability, and expression of selectins and integrin ligands, which allows neutrophils, macrophages, and T lymphocytes to enter into extravascular spaces , . They also affect physical interactions between B and T cells in secondary lymphoid organs, leading to production of cytokines and antibodies  .
On the other hand, PGs are often associated with anti-inflammatory activities such as inhibition of mediator release from macrophages, neutrophils, mast cells, basophils, and lymphocytes. Thus, they can also downregulate macrophage functions  . PGE 2 also has potent proinflammatory effects leading to the classic signs of inflammation such as fever and pain. In addition, PGE 2 has other anti-inflammatory effects such as suppression of lymphocyte proliferation and inhibition of production of certain types of cytokines. Accordingly, PGE 2 plays a role in starting inflammatory processes and in their resolution. However, both the proinflammatory and anti-inflammatory roles of prostanoids depend on the nature of the inflammatory stimulus and the specific prostanoid produced  ([Table 1]). Hence, prostanoids may be considered as main factors in the regulation of coagulation and local blood flow, which may be of importance at the site of parasitic invasion  .
| Prostanoids and parasites|| |
PGs may play a part in the pathogenesis of parasitic diseases  . Although generally invertebrates lack de-novo synthesis of polyunsaturated fatty acids and prostanoids, parasites have been shown to generate PGs and TXs  . In addition, because all invertebrates cannot synthesize the precursors of prostanoids, they acquire their polyunsaturated C 20 -fatty acids and AA from the abundant supply available in cellular membranes of mammalian cells, human plasma, and lymph. During inﬂammation, AA is released from phospholipids by activity of PLs. Parasite enzymes metabolizing prostanoids are poorly characterized. In helminths, COXs as central prostanoid-metabolizing enzymes, have not been detected. On the other hand, glutathione S-transferases (GST), also known to catabolize eicosanoids to PGs, have been demonstrated to express PG synthase activity in nematodes  . Recently, another report indicated that a number of parasitic organisms such as E. histolytica and Trypanosoma spp. produce PGs in the same way as their mammalian hosts and by similar enzymatic mechanisms  .
In 1995, the mechanisms of impairment of cell-mediated immunity in invasive amoebiasis were assessed. Macrophages treated with soluble amoebic proteins suppressed the induction of IFNγ-induced surface Ia antigen molecule expression by 30-61% but had no effect on surface Ia molecules already expressed. It was concluded that E. histolytica suppresses IFNγ-induced macrophage surface Ia molecule synthesis and I-A beta mRNA expression by stimulating the production of PGE 2 , which is important for immunoregulation. The breakdown of macrophage function via PGE 2 biosynthesis is a new way by which the parasite inhibits host defenses  . In amoebic liver abscesses, E. histolytica also induces COX-2 expression in macrophages  with subsequent production of prostanoids.
In 2001, another study was conducted to assess whether colonic amoebiasis induces the expression of COX-2 and to determine the contribution of PGs to the host response. The researchers infected human fetal intestinal xenografts subcutaneously implanted in susceptible mice with E. histolytica. The results showed that colonic amoebiasis induces the expression of COX-2 in both epithelial cells and macrophages. Moreover, PGs produced through COX-2 enhanced neutrophil response to infection and epithelial permeability. Treatment of mice with indomethacin (COX-2 inhibitor) decreased PGE 2 levels and caused neutrophil infiltration  .
Two years later, it was concluded that COX-like activity and immunoreactive proteins were present in the nuclear fraction of E. histolytica. Little homology existed at the nucleotide and amino acid levels between the amoebic COX and COX-1/2 enzymes from different species. The AA-binding domain and heme-coordinating and catalytic sites present in other species were absent in amoeba. Amoeba COX expressed in Escherichia More Details coli demonstrated COX-like enzyme activity in vitro by converting AA into PGE 2 but not into PGD 2 or PGF 2a . The authors added that COX activity was inhibited with 1 mmol/l aspirin. Thus, it was concluded that E. histolytica produces PGE 2 by means of a previously undescribed ancestral COX-like enzyme and that PGE 2 plays a main role in pathogenesis and immune evasion of the organism  .
In a study conducted by Lejeune et al.  , the pathological role of E. histolytica-derived PGE 2 in the onset of diarrhea was established. It was reported that amoeba-derived PGE 2 alters ion permeability of paracellular tight junctions (TJs) in colon epithelium. This loss of mucosal barrier integrity corresponds with increased ion permeability across TJs. The authors added that the significant alteration of TJ protein (claudin-4) leads to increased sodium ion permeability through TJs toward the lumen with increased luminal chloride secretion. Thus, the NaCl gradient, created across epithelia, could serve as a trigger for the osmotic water flow that leads to diarrhea.
It was also shown that PGE 2 produced by live amoebae acts as an IL-8-stimulating molecule. This was proved by treating trophozoites with COX inhibitors resulting in inhibition of PGE 2 biosynthesis and IL-8 production. The initiation and ampliﬁcation of acute inﬂammation associated with intestinal amoebiasis was explained by the binding of PGE 2 through the PG receptors 'EP4' in colonic epithelial cells. This results in stimulation of potent neutrophil chemokine and activation of IL-8 production leading to acute host inﬂammatory response. Hence, it was recommended that EP4 antagonists targeting receptors are potentially therapeutically important in the treatment of amoebiasis  .
Using a suckling rat model, it was shown that malabsorptive syndrome occurs in cryptosporidiosis without involvement of PGs. Rather it was reported to be due to impairment of electrogenic transport across the ileal mucosa, as well as transcellular and paracellular permeability and leucine and glutamate absorption  . One year later, Gookin et al.  showed that PGs actually play a central role in regulating intestinal fluid secretion in animal models of cryptosporidiosis; PGE 2 and PGI 2 were found at higher concentrations in infected tissues. This increased mucosal PG production leads to increase in calcium and cAMP, which inhibit neutral NaCl absorption. Consequently, this results in decreased paracellular water absorption by the villus, stimulation of anion secretion, and secretory diarrhea. It was further reported that PGI 2 might act on components of the enteric nervous system by stimulating the nicotinic ganglia and cholinergic motor neurons that innervate the intestinal mucosa, whereas PGE 2 acts directly on enterocytes  . It was also shown that mesenchymal epithelial cells in the lamina propria as well as infiltrating and resident leukocytes in the mucosa (e.g. macrophages) have a role in producing high levels of PGs during cryptosporidiosis  . However, inhibition of neutrophil migration into infected tissue proved to have no effect on PG synthesis  . Meanwhile, it was demonstrated that treatment of infected or inflamed mucosa with a PG synthesis inhibitor will restore normal electrolyte transport and water despite the villous atrophy, showing that the transporters are fully functional, even in the immature enterocytes , .
On the other hand, Gookin et al.  showed that cryptosporidiosis is associated with increased synthesis of nitric oxide (NO), PGE 2 , and increased mucosal permeability. This was shown by the nonselective inhibition of NOS (NG-nitro-L-arginine methyl ester) that inhibited PG production, leading to a greater increase in paracellular permeability. Baseline permeability was also restored in the absence of NO by exogenous PGE 2 . The mechanism by which PGE 2 causes epithelial barrier function of C. parvum-infected mucosa is not clearly understood but it was hypothesized that it may involve the maintenance of paracellular space closure rather than have a direct effect on the epithelium  .
Later, it was demonstrated that NO serves as a proximal mediator of PGE 2 synthesis and epithelial barrier function in cryptosporidiosis. Reactive nitrogen species have also been demonstrated to activate COX enzymes and stimulate PG-mediated secretion when NO production is augmented by arginine supplementation , . As indicated, this in turn increases the severity of infection with subsequent increase in epithelial chloride secretion and diarrhea. Epithelial secretion by infected mucosa from L-arginine-supplemented piglets was fully inhibited by the COX inhibitor indomethacin, indicating that PG synthesis was responsible for this effect  .
Current knowledge regarding the role of prostanoids in giardiasis is scarce. The synthesis and metabolism of phospholipids and fatty acids in G. lamblia was first investigated by Jarroll et al.  almost three decades ago, and it was postulated that Giardia spp. had little or no ability to synthesize its own lipid molecules de novo. Ellis et al.  failed to detect lipid-bound AA, the precursor of PGG 2 synthesis, in Giardia trophozoites, suggesting that it might be present only in trace amounts.
In 2000, it was found that radiolabeled bases such as choline, inositol, ethanolamine, serine, and glycerol become incorporated into phospholipids of trophozoites when added to the culture medium. Thus, it was concluded that G. lamblia trophozoites colonized in the small intestine utilize preformed lipids and fatty acids from the lipid-rich environment. Many of these exogenous lipids/fatty acids were reported to undergo remodeling before they were incorporated into giardial membranes , . This fact was supported by finding that radiolabeled fatty acids are directly incorporated into membrane phospholipids, suggesting that Giardia spp. might have many cellular mechanisms to form new phospholipids  . Special procedures, as in the Lands cycle, were used by G. lamblia to obtain lipids, such as through deacylation/reacylation reactions. This led to the conclusion that lipid remodeling pathways play key roles in regulating the growth and differentiation of Giardia spp., thus presenting a potential drug target  .
The established genome database (http://www.giardiadb.org), which includes the Giardia genome, and Morrison et al.  revealed the presence of metabolic genes and lipid synthesis. The researchers also added that there are several classes of phospholipid-transport, ATPases, or flippases (FLIPs) that allow Giardia spp. to uptake aminophospholipids efficiently from the environment of the small intestine. Genomic and lipidomic data obtained in another study indicated that Giardia spp. change lipids taken from the environment by base-exchange reactions to synthesize fatty acids, phospholipids, and neutral lipids. It was postulated that two of the major phospholipids, phosphatidyl-glycerols and phosphatidylethanolamines, might be produced via base-exchange reactions, suggesting that the parasite could synthesize prostanoids from its phospholipid pool and that these two mediators may play a role in the pathogenesis of giardiasis  .
However, in spite of the expression of five sphingolipid metabolic genes, Giardia spp. was found to exhibit limited lipid synthesis capacity de novo, where it obtains ceramide and sphingolipids from its host for growth, survival, and encystation  . Therefore, it was concluded that products of gspt and gglct-1 genes are important for cellular functions rather than for the synthesis of new sphingolipids, and that blocking the latter results in decreased growth and Giardia encystation. It remains to be seen whether Giardia spp., like other parasites, are capable of synthesizing eicosanoids or PGs ,, .
In vivo studies regarding the role of prostanoids in trichomoniasis are limited. In a study by Shaio et al.  , the possibility that prostanoid production by trichomonads is responsible for neutrophil activation was observed. Leukotriene B 4 , which is produced by leukocytes during inflammation, but not TXB 2 or PGE 2 , is generated by T. vaginalis, indicating that T. vaginalis could follow a different AA-metabolic pathway than that of mammalian cells.
Sayed et al.  linked T. vaginalis pathogenesis with cervical cancer. The enhanced synthesis of PGs induced by COX-2, which is often upregulated in many inﬂammatory diseases, stimulates cancer cell proliferation  , inhibits apoptosis, and promotes angiogenesis  . The overexpression of COX was recorded in various cell types of primary and metastatic epithelial cancers, including prostate and cervical cancers  . It was postulated that a similar situation might be present during trichomoniasis as in H. pylori infection, which is in turn linked to gastric cancer  .
In the year 2005, the first study to understand the basis of interaction of trichomonads with host cells and the corresponding host responses triggered by the parasites was conducted by Kucknoor et al.  . The researchers analyzed COX-2 protein expression by T. vaginalis using western blot and immunofluorescence assays. They showed that p38 mitogen-activated protein (MAP) kinases and tyrosine kinases play a role in COX-2 induction. The authors added that T. vaginalis and Tritrichomonas foetus but not Pentatrichomonas hominis possess some soluble factors that induce COX-2 gene expression and that COX-2 may also be induced by the upregulation of cytokines and other growth factors that are initiated by T. vaginalis adherence. It was suggested that COX-2 induction is important for the pathogenesis of T. vaginalis. However, several recent studies did not confirm the association between T. vaginalis and cervical cancer. Two studies determined that T. vaginalis might be a concomitant infection with high-risk human papilloma virus infection and other cervical cytological abnormalities and thus should not be considered influential in predisposing to cervical cancer , .
The role of PGs in the infection of mouse macrophages by L. amazonensis was assessed. The results showed that macrophage infection by Leishmania spp. is enhanced by PGs produced by macrophages  . Previous studies reported that PGE 2 production associated with leishmaniasis might favor Leishmania spp. persistence and progression , . Pérez-Santos and Talamás-Rohana  added that treatment with indomethacin enhanced the intracellular killing of L. mexicana parasites in infected BALB/c mice. They concluded that indomethacin suppressed PGs promoting the development of a protective Th1 type response in susceptible mice by enhancement of IL-12, IFN-γ, and NO production.
It has also been shown that Leishmania spp. induce the production of the inflammatory lipid mediator PGE 2 from macrophages ,, , leading to the successful survival of the parasites inside the host cells. In confirmation, it was found that wild-type mice treated with indomethacin, an inhibitor of PGE 2 synthesis, during the first 3 weeks of L. amazonensis infection developed smaller lesions and lower parasitic load when compared with the control group. The lesion of indomethacin-treated groups consisted of macrophages without vacuoles and small or absent necrotic areas, indicating that PGE 2 is a susceptibility factor to L. amazonensis infection. Although PGE 2 leads to inhibition of mechanisms responsible for destruction of the L. amazonensis parasite, the deficiency of this factor is not enough to cure infection. Thus, it has been suggested that a direct inhibitory action is exerted in the macrophages by the parasite, and/or the participation of other factors in mediating susceptibility/resistance to L. amazonensis infection exists , .
It was demonstrated that the HIV-1 Tat protein enhances Leishmania replication in human macrophages. Leishmania spp. growth doubled in HIV-1-infected macrophages and the anti-Tat antibody decreased the protozoan replication by 70%. Tat enhanced COX-2 expression and PGE 2 production, and a COX-2 inhibitor abolished the Tat-mediated augmentation of Leishmania replication. Moreover, PGE2 increased Leishmania spp. growth, which was stopped by anti-transforming growth factor (TGF)-β1 monoclonal antibodies  .
In 2008, the in vitro and in vivo effect of PLA 2 on experimental cutaneous leishmaniasis was investigated. The study showed that PLA 2 may cause extension of cutaneous leishmaniasis by suppressing the effect on IL-2 levels and the generated PGE 2  . It was concluded that L. major infection might lead to polarization of T cells to Th2 through PGE 2  .
Later in 2012, a study was conducted to assess the effect of glycyrrhizic acid and its immunomodulatory potential in a model of experimental visceral leishmaniasis. Results showed that glycyrrhizic acid treatment increased macrophage effector responses through inhibition of Cox-2-mediated PGE 2 release in L. donovani-infected macrophages  . In another study conducted in 2013, Díaz-Gandarilla et al.  found that 6k-PGF 1α, PGE 1 , and PGF 1α production increased, whereas both PGE 2 and PGF 2α production decreased after Leishmania spp. infection, and increased in treated and infected macrophages. They added that use of peroxisome-proliferating activated receptor (PPAR) promoters and anti-cPLA 2 diminished 6k-PGF 1α, PGE 1 , and PGF 1α production after Leishmania spp. infection. It became clear that PGE 2 is able to inhibit COX-2 expression in the presence of these proinflammatory cytokines and that cPLA 2 inhibition also inhibits COX-2 expression through PPARγ  . All these results may explain why, during PPARγ activation, PGE 2 production was found to be increased by macrophages infected with L. mexicana  .
In a study by Penke et al.  , the contribution of four PG receptors EP1, EP2, EP3, and EP4 to infection with Leishmania spp. was investigated. Authors reported that L. major enhanced EP1 and EP3 expressions but reduced EP2 and EP4. Treatment of L. major-infected susceptible BALB/c mice with EP1 and EP3 antagonists or treatment with EP2 and EP4 contenders resulted in significant reduction of parasites in the draining lymph node. This observation revealed the selective targeting of PGE 2 receptor as a main therapeutic agent. The researchers added that diminution of EP2 and EP4 expression may represent one of the parasite's immune evasion strategies  .
It was found that the interaction of T. gondii with platelets resulted in marked increase in TXB 2 production. TX plays a role in platelet-induced cytotoxicity. Both the TXA 2 -generating platelet microsome system and stable TXA 2 correspondents cause damage to Toxoplasma spp. cellular membranes. Thus, it was deduced that involvement of platelets in the host defense against T. gondii is by release of both TX types, which may be important in this cytolytic process  . In addition, it was found that tachyzoites cause a noticeable change in prostanoids released by human mononuclear phagocytes. Adherent human monocytes isolated after 2 h of culture released both TXB 2 and PGE 2 and leukotriene products when stimulated by heat-killed tachyzoites. However, after 5 days the monocytes lost their ability to release TXB 2 and PGE 2  .
In 1995, a study evaluated the role of human granulocyte-macrophage colony-stimulating factor (GM-CSF) in the static activity of Toxoplasma spp. and in the production of H 2 O 2 and PGE 2 by human monocytes. Results showed that incubation of monocytes from healthy controls with GM-CSF led to a dose-dependent decrease in Toxoplasma static activity and H 2 O 2 production. GM-CSF-treated monocytes produced more PGE 2 compared with untreated cells. Furthermore, incubation of these cells with indomethacin resulted in a reduction in PGE 2 release and return of Toxoplasma static activity. It was concluded that GM-CSF decreases Toxoplasma static activity of monocytes through production of PGE 2  .
Macrophages invaded by T. gondii are also involved in PGE 2 synthesis where the parasite was reported to regulate macrophage functions by regulating AA production through a calcium-dependent pathway and induction of COX-2 expression. This leads to increased release of immunosuppressive molecules PGE 2 , in macrophages in a time-dependent manner  . In other cell types, studies showed that enzymatic conversion of AA into PG down modulates the cell-mediated immune response allowing survival of both intracellular pathogens and the host , .
An in vivo study showed that, during acute infection of mice with T. gondii, inflammatory monocytes were associated with production of the lipid mediator PGE 2 . These monocytes could also inhibit neutrophil activation in a PGE 2 -dependent manner. Moreover, mice developed severe neutrophil-mediated pathological reactions in the absence of inflammatory monocytes, which was controlled by analogous PGE 2 treatment. On the other hand, inhibition of PGE 2 led to increased neutrophil activation with a high mortality rate. Thus, inflammatory monocyte-derived PGE 2 can be considered to be at the center of a regulatory mechanism that is important for control of host-pathogen-induced inflammation. The researchers concluded that modulation of the PGE 2 metabolism may represent an important future therapeutic approach in the management of many inflammatory and infectious diseases  .
Another recent study attempted to test the role of the macrophage migration inhibitory factor (MIF) proinflammatory cytokines in the production of the mediator PGE 2 and on the susceptibility of Toxoplasma spp. in in vitro-infected human trophoblast BeWo cultured cells. Results showed that treatment with low concentrations of MIF increased the production of PGE 2 , whereas treatment with high concentrations controlled the parasites. Treatment with tachyzoite-soluble antigen also did not alter PGE 2 release. The researchers concluded that PGE 2 is an important factor for the persistence of T. gondii at the maternal-fetal interface and that MIF is unable to control toxoplasmosis at low concentrations. The expression of activated PGE 2 reflects its efficiency as a mediator in promoting parasite proliferation  .
Infection of skeletal muscle cells with T. gondii also promotes modulation of PGE 2 production and COX-2 gene induction. Recent research showed that certain factors led to the establishment and preservation of infection by T. gondii in the muscle tissue causing chronic toxoplasmosis. These factors comprised the close association between the parasitophorous vacuole and the sarcoplasmic reticulum and lipid droplets, providing a source of lipids and other nutrients for the parasite's survival, as well as increased levels of IL-12, INF-γ, and the inflammatory indicators PGE 2 and COX-2  .
As with the above observation in toxoplasmosis  , Melo et al.  had reported earlier that lipid bodies and lipid-rich inclusions present in inflammatory cells may have a role in prostanoid production in Chagas disease. Recently, it was demonstrated that lipid bodies in macrophages are the sites of PGE synthesis. The fatty acid synthase inhibitor C75 was found to inhibit lipid body biogenesis by reversing the effect of apoptotic cells on lipid body formation, prostanoid synthesis, and parasite replication. These findings demonstrated the role of the highly regulated lipid bodies in releasing PGE 2 lipid mediator by macrophages, indicating that they are potentially involved in Trypanosoma cruzi immune evasion mechanisms  .
Another comparative study showed that the mediators PGF 2a , 6-keto-PGF1a, and TXB 2 could be mainly associated with protective mechanisms in acute infection but seem not to be involved in its maintenance in the chronic infections  . In contrast, it was suggested that PGs mediate the immunosuppression observed in the acute phase of Chagas disease  .
It was also reported that TXA 2 , which is the predominant prostanoid present in all life stages of T. cruzi, is released by infected human endothelial cells. Parasite-derived TXA 2 accounts for the majority of its circulating levels in infected wild-type mice, and affect host physiology. Deficiency of the TXA 2 gene receptor in mice resulted in higher mortality and more severe parasitism and cardiac pathology compared with wild-type mice. It was concluded that the host response to parasite-derived TXA 2 in Chagas disease may prove to be an important regulator of parasitism and mortality, which may enhance its future use as a novel therapeutic target  .
The role of PGE 2 in cardiac lesions caused by Chagas disease was investigated in 2008. It was observed that treatment with COX-2 inhibitors decreased the synthesis of PGE 2 by spleen cells, which was accompanied by reduced numbers of parasites, infiltration by inflammatory cells, and cardiac fibrosis. The researchers concluded that treatment with COX-2 inhibitors leads to inhibition of PGE 2 synthesis and reduction of cardiac damage observed during the acute phase of experimental Chagas disease  . On the other hand, it was shown that prostanoids may be involved in oxidative stress in host defenses against this disease. Induced production of COXs-mediated PGs is considered a basic mediator in the control of parasite burden and erythrocyte oxidative stress during infection by T. cruzi in mice  . In Wistar rats with immunosuppression due to infection with T. cruzi, the combined treatment with melatonin and meloxicam significantly enhanced the blockage of PGE 2 synthesis, release of IL-2 and IFN-γ into the animals' serum, and release of NO by macrophages. As a result there was significant reduction in parasitemia  . An attempt to evaluate the effects of 15d-PGJ 2 administration during the acute phase of infection in mice showed decreased inflammatory infiltration in skeletal muscles, decreased number of white blood cells, and decreased density of amastigotes in cardiac muscle. This was associated with a statistically significant increase in IL-10 levels and no change in IFN-γ levels. It was concluded that treatment with 15d-PGJ 2 in the acute phase of Chagas disease enhanced immune response and decreased numbers of amastigote collections  . In COX-1-null mice infected with the Brazil strain of T. cruzi, Mukherjee et al.  studied the effects of aspirin on the parasite and host biosynthetic pathways. Aspirin treatment diminished parasite-derived and host-derived circulating PGs with subsequent increase in mortality and parasitemia. However, there was no significant differences in histopathology or cardiac structure or function. Delayed treatment with aspirin did not increase parasitemia or mortality but improved ejection fraction of the heart. The infected COX-1-null mice exhibited reduction in circulating levels of TXA 2 and PGF 2α with increased parasitemia as compared with aspirin-treated infected mice, indicating that the effect of aspirin on mortality had little to do with inhibition of PG metabolism. In a more recent study, treatment of macrophages with either NOS inhibitors or PGE 2 restored the invasive action of T. cruzi in macrophages previously treated with aspirin. The results of this study indicated that PGE 2 , NO, and lipoxins are involved in regulation of anti-T. cruzi activity by macrophages. This clarified the role of PGs in the innate inflammatory response to Chagas disease, and presented the possibility of future research in specific immune intervention  . Another report indicated that T. cruzi infection in mice induces myocardial gene expression of Cox-2 and TX synthase. The parasite's collaboration with the endothelial vasoconstricting peptide (ET-1) activates the Ca 2+ /calcineurin (Cn)/nuclear factor of activated T-cells signaling pathway in atrial myocytes. This leads to COX-2 protein expression and increased release of PGE 2 and PGF 2α, TXA 2 eicosanoids  .
Other reports also showed that many changes that occur during acute and chronic Chagas disease can be accounted for by the effects of prostanoids such as PGs and TXs. This was demonstrated by the treatment with COX inhibitors during acute infection that led to increased parasite load and mortality, whereas treatment during chronic infection beneficially led to improvement in cardiac function and decreased mortality. The majority of TXA 2 liberated during Chagas disease is derived from the parasite. TXA 2 is a potent vasoconstrictor that contributes to the pathogenesis of the associated cardiovascular disease. It may also control parasite differentiation and proliferation, allowing the infection to progress to a chronic state. It was concluded that the same mediators that initially ensure host survival may later cause cardiovascular damage  . Thus, as indicated, prostanoids may be considered as prospective targets for treatment of Chagas disease  . Moreover, studying T. cruzi-infected neonatal cardiac cells, researchers considered 15d-PGJ 2 to be a potent modulator of the inflammatory process and regulator of parasite growth through PPARg-dependent and PPARg-independent (Erk-MAPK and NF-kB) pathways. It was found that calcium-independent PLA2g (iPLA2g) accounts for the majority of PLA 2 activity and is responsible for AA and PGE 2 release in rabbit ventricular myocytes. This study demonstrated that T. cruzi infection activates iPLA2g in cardiac muscle cells, which results in increased release of AA and PGE 2 mediators that may be essential for host survival during acute infection. Thus, iPLA2g acts as a cardioprotective agent during the acute stage of Chagas disease  .
Mukherjee et al.  provided evidence that epimastigotes, trypomastigotes, and amastigotes of T. cruzi express a biologically active prostanoid-like receptor mainly present in their flagellar membranes. This receptor is similar to TP receptors in human platelets.
Other research attempted to evaluate the role of monocytes as essential sources of PGE 2 inflammatory mediators in Chagas disease patients. In this trial, peripheral blood mononuclear cells (PBMCs) before and after depletion of monocytes from patients with Chagas disease and from noninfected individuals were evaluated. It was found that partial depletion of adherent cells decreased production of PGE 2 slightly in patients with Chagas disease. Thus, monocytes seem to be important for modulation of immune responses in Chagas disease by inflammatory mediators and by regulating the processes of inflammation and antigen presentation  .
It was shown that T. brucei produces PGs in plasma and cerebrospinal fluid, producing fever, headache, immunosuppression, deep muscle hyperesthesia, miscarriage, ovarian dysfunction, and sleepiness. PGF 2a was the major prostanoid produced by T. brucei trypanosome lysates (TbPGFS). Phylogenetic analysis and molecular properties demonstrated that TbPGFS is completely distinct from mammalian PGF synthases. The researchers also found that TbPGFS mRNA expression and TbPGFS activity were high in the early logarithmic growth phase and low during the stationary phase  . It was reported that TbPGFS catalyzes the NADPH-dependent reduction of 9,11-endoperoxide PGH 2 to PGF 2a , and leads to elevation of PGF 2 concentration during African trypanosomiasis  . Prostanoids produced by African trypanosomes such as PGD 2 , PGE 2 , and PGF 2a probably interfere with the host's physiological response. However, addition of PGD 2 to cultured trypanosomes led to a significant inhibition of its growth, whereas PGE 2 or PGF 2a did not have the same effect. Trypanosomal PGD 2 induces an apoptosis-like programmed cell death (PCD) including maintenance of plasma membrane integrity, phosphatidylserine exposure, loss of mitochondrial membrane potential, nuclear chromatin condensation, and DNA degradation  . Having found that PGD 2 induces PCD of T. brucei in the bloodstream, Figaralla et al.  attempted to investigate further whether it is PGD 2 or its J series of metabolites that are the main cause. They concluded that PGJ 2 and ∆ 12 PGJ 2 metabolites of PGD2 in serum increased intracellular reactive oxygen species and enhanced PCD of trypanosomes.
As with T. cruzi, in malaria, pathogenesis and symptoms are mediated by prostanoids and COX-2-derived PGs, which are the important proinflammatory mediators of the host-immune response. Bicyclo-PGE 2 and COX-2 proteins were found to be lower in children with mild and severe malaria in comparison with healthy children. Accordingly, it was deduced that, in healthy children exposed to malaria, elevated PGE 2 may protect them against the infection and that decrease in PGE 2 induced by IL-10 during acute malaria may increase susceptibility to severe disease  . An attempted study of the effect of suppressing circulating bicyclo-PGE 2 in malaria-infected children and those with additional bacteremia or HIV infections revealed its significant association with reduced hemoglobin levels. The authors concluded that bicyclo-PGE 2 may be considered as a marker and as a mediator of pathogenesis in malaria  .
Study of PG in patients recovering from P. falciparum infection revealed three groups of classified prostanoid groups. Group 1 was composed of four subgroups; group 2 was composed of three subgroups that were unrelated to symptoms during the recovery process; and group 3 TXB 2 was increased per chance due to platelet regeneration and recovery, whereas 8-epi PGF 2α was decreased possibly because of high oxidative stress  . Furthermore, decreased COX-2/PGE 2 levels were found to be significantly associated with increase in IL-10 anti-inflammatory cytokine, responsible for expression of COX-2 gene products. Also suppression of COX-2/PGE 2 is caused by the ingestion of ferriprotoporphyrin by blood mononuclear cells. Thus, the acquirement of hemozoin by blood mononuclear cells in malaria accounts for suppression of PGE 2 by inhibiting molecular de novo COX-2 transcripts  .
Another report confirms that malarial pigment and malarial parasite products ingested by blood mononuclear cells induce suppression of PGE 2 through suppression of COX-2. It was noted that enhanced malarial anemia is associated with suppression of PGE 2 allowing overproduction of Tumor Necrosis Factor (TNFα)  . The relation of free heme and the suppression of anti-inflammatory mediators such as PGE 2 in human vivax malaria have been investigated. Patients with severe disease with higher hemolysis had lower plasma concentrations of PGE 2 than those with mild disease. This was attributed to the increased concentrations of plasma PGE 2 that occurred in severely sick patients undergoing treatment. Therefore, it was deduced that the binding of heme to CD14 monocytes, induced partial impairment of PGE 2 production. The researchers assumed that these results may generally explain the mechanisms of hemolytic diseases and represent a basis for future studies on therapeutic approaches  . On the other hand, PGD 2 , which is a potential factor derived from P. falciparum within erythrocytes, may be involved in the pathogenesis of cerebral malaria by inducing heme oxygenase-1 expression releasing iron, carbon monoxide, and biliverdin/bilirubin, and may influence iron supply to the P. falciparum parasites  . Another report also showed that in children with cerebral malaria and severe anemia there is significant reduction of PGE 2 in plasma and urine and COX-2 transcripts, with significant positive association between hemoglobin and both plasma and urinary PGE 2 . Additional analyses demonstrated the progressive decrease of plasma and urinary PGE 2 and COX-2 transcripts with the increase in concentration of malarial pigment in monocytes. It was concluded that reduced COX-2-derived PGE 2 decreased erythropoietic responses in children with severe malaria  .
In 2000, the ability of the filarial parasite O. volvulus to compete with serum albumin for procurement of the AA precursor of prostanoids was evaluated. Results showed that the worm's secretory protein (OvS1) bound AA with a five-fold greater affinity than that of the main host's fatty acid carrier protein  . A later study reported that O. volvulus carries extracellular GST (Ov-GST1), which is a glutathione-dependent PGD synthase, in its outer hypodermal lamellae and in parts of the cuticle. This Ov-GST1 produces PGD2 directly at the parasite-host interface  . In another report it was hypothesized that the large amount of AA surrounding the parasite may promote the uptake of fatty acid important for PG synthesis. The researchers conceded that the mechanisms controlling inﬂammatory processes in onchocerciasis facilitate the survival of the parasite, leading to chronic infection. They explained that the synthesized PGE 2 promoted the production of IgE and IgG1 in mice  , corresponding to human IgG4  , and that both antibody types, which are characteristic of Th2-type immune responses, are characteristic of onchocerciasis  .
An immunohistological study to depict the site of PGE 2 in adult male and female O. volvulus showed signiﬁcant localization in the hypodermis and weak expression in the epithelia of the intestine, uterus, and male genital tract, while the muscles stained PGE 2 negative. Less-pronounced PGE 2 staining was observed in some dermal microﬁlariae. It was concluded that PGE 2 released from live or dead ﬁlaria worms could affect the host´s immune response and metabolism in favor of the filarial parasite  .
In 2008, it was shown that the GST of Ov-GST1 carries a signal peptide that is cleaved off during maturation of the worm. This glycoprotein enzyme is probably involved in the production of parasite-derived prostanoids that control the host's effector responses, and thus it may be considered a target for chemotherapy and vaccine development  .
A more recent study on the onchocercoma showed that PGE 2 occurred significantly in infiltrating inflammatory cells. Sequential sectioning revealed the additional presence of TGF-β with PGE 2 . The authors indicated that the concomitant infiltration of PGE 2 and TGF-β immunoregulative mediator in host cells may control the inflammatory responses favoring the survival of the filarial worms  .
It was previously noted that microﬁlariae of W. bancrofti and B. malayi while circulating in the blood acquire polyunsaturated fatty acids, AA, and other fatty acids, and discharge PGE 2 on their surface  . Further, inhibition of aggregation of human platelets by microfilariae was evaluated in vitro. It was found that B. malayi microfilariae incubation with human platelets inhibited their aggregation, as well as TX generation and serotonin release. This inhibition did not require direct contact with the parasites and was found to be stimulated by thrombin, collagen, and AA. Decreased release of PGI 2 and PGE 2 and consequent inhibition of platelet aggregation occurred after treatment of microfilariae with COX inhibitors. These results confirmed the role of antiaggregatory prostanoids released by microfilariae in enhancing their survival  . Dirofilariasis in naturally infected cats showed significantly higher levels of PGE 2 and TXB 2 than in uninfected cats. This led the researchers to specify that dirofilariasis leads to the production of intravascular prostanoids, where PGE 2 in the early phase of infection may promote worm survival, whereas TXB 2 detected later may mediate inflammatory responses and thrombi formation  .
An early report in 1984 revealed the involvement of PGs during cercarial skin penetration due to stimulation of cercariae by skin and fatty acids. The researchers based their findings on the prevention of this response by COX inhibitors (ibuprofen and aspirin and 13-azaprostanoic acid) as powerful antagonists of the TX/endoperoxide receptor  .
In another early report, it was shown that macrophages from S. mansoni liver granulomas of mice could synthesize TXA 2 in larger amounts than PGE 2 and PGI 2 . Thus, TXA 2 appeared to be the major AA metabolite produced after stimulation of cells by either a phagocytic stimulus such as zymosan or by exogenous substrates AA and PGH 2 . It was concluded that TX synthase is responsible for the main arachidonate enzymatic activity in these cells  . In another study, the formation of PGE 2 by human PBMCs in schistosomiasis patients via the L-arginine-NO pathway concluded that NO too may be another important second signal stimulating PGE 2 production by immune complexes in PBMCs  . In a later report, after incubation with linoleic free fatty acid, which naturally occurs on the surface of the skin, S. mansoni cercariae were found to produce significant quantities of PGE 2 . COX-2 inhibitors failed to block this reaction, indicating that production of PGE 2 by the cercariae may be through a different biochemical pathway. In addition, the cercariae could induce PGE 2 and IL-10 from human and mouse cultured keratinocytes cells, which were not blocked by COX-2 inhibitors. In sharp contrast, the induction of PGE 2 or IL-10 from skin cells was significantly reduced after attenuation of cercariae by gamma irradiation. In the absence of IL-10 the schistosomula in the skin became surrounded by a noticeable cellular reaction that hindered migration through the skin. It was therefore postulated that the cercarial-induced PGE2 is involved in downregulation of host immune responses in the skin  . It was also found that the production of PGD 2 by S. mansoni interferes with migration of Langerhans cells TNFα through the adenylate cyclase-coupled PGD 2 receptor causing reduction of contact hypersensitivity responses. Accordingly, this inhibition of Langerhans cell migration may be another means for evasion of the host immune system by the parasites. Thus, PGD 2 too may have a major function in maintaining the cutaneous immune response against schistosomiasis  .
Another study found that PGE 2 secretion from mouse macrophage model cells was significantly promoted and IFN-γ-induced major histocompatibility complex (MHC II) expression was significantly suppressed by antigen prepared from normal cercariae as compared with antigen prepared from ultraviolet-radiation-attenuated cercariae  .
In addition, the activation of hepatic stellate cells, which particularly affects schistosome-induced hepatic fibrosis, could be inhibited by PGE 1 by alternating type I and III collagen. The researchers indicated that PGE 1 effectively protects the liver from fibrosis and that its combination with praziquantel therapy would effectively reverse ensuing fibrosis  .
Thanan et al.  used immunohistochemical analysis to study stem cell markers (Oct3/4 and CD44v6) and COX-2 expression in urinary bladder tissues from cystitis and cancer patients. The Oct3/4 stemness marker showed significantly higher immunoreactivity in S. haematobium-infected tissues than in normal tissues; whereas COX-2 located in the nuclei upregulated the two stemness markers in the presence of schistosomiasis-associated urinary cancer than in normal tissues. This proved enhancement of stem cell proliferation and differentiation through the production of PGE 2 , which in turn promotes inflammation of the urinary schistosomiasis.
As with the other parasites mentioned, prostanoids were found to affect the pathophysiological changes in fasciolosis by acting as a cytoprotective and anti-inﬂammatory agent  . It was observed that the reduction of prostanoid and increase in TXB 2 /PGI 2 levels occur similarly in both F. hepatica infection and alcoholic liver disease  .
It was explained that reduction of prostanoid produced by F. hepatica may be a result of inhibition of PL activity, enhanced catabolism, and/or negative feedback of prostanoid. Such a decrease in the level of PGE 2 may then predispose to Fasciola-associated hepatitis and fibrosis. Parasite-induced inflammatory vascular responses such as vasoconstriction or vasodilation may be due to PGs such as TXB 2 and PGF 2α or PGI 2 and PGE, respectively. On the other hand, prostanoids of parasite origin may inhibit macrophages and T-cell and B-cell functions allowing its evasion of the host's immune system  . The pattern of plasma prostanoids was also studied during the course of acute and chronic fasciolosis in sheep. This revealed a reduction in plasma PGE 2 and a significant increase in TXB 2 over PGF 1 . The surmised indication was that the shift in ratio causes altered clotting of blood during fasciolosis as TXB 2 stimulates thrombocyte aggregation, whereas PGI 2 is anti-aggregatory. The suspected cause for reduced plasma PGE 2 was its probable enhanced catabolism or disturbed synthesis of PG in the liver. It was concluded that parasite-induced liver damage is the cause of prostanoid depletion in the plasma, and prostanoid levels correlate with the severity of liver injury and clinical signs of fasciolosis. Furthermore, it was deduced that parasite-derived prostanoids enable the flukes to develop and survive and at the same time enhance the associated fibrosis in the parasitized bile ducts  .
Assessment of the plasma levels of PGE 2 , 6-keto-PGF 1a , and TXB 2 in F. hepatica infections of water buffaloes was also attempted. Transient increase in plasma PGE 2 was noted in buffaloes with subclinical fasciolosis. However, throughout the study period, no statistically signiﬁcant increase was recorded, indicating that the early phase of subclinical fasciolosis is not associated with changes in plasma PGE 2 levels. On the other hand, during chronic fasciolosis, TXB 2 values showed transient significantly lower values. Even then the detected moderate changes in plasma prostanoid patterns might still be responsible for tissue damage and/or inflammation with F. hepatica infection. The different PGE 2 responses in infected sheep and water buffaloes may be attributed to differences in the course of infection and in the host's resistance. In water buffaloes, the recorded low fluke burden indicated the unlikely direct involvement of the worm products in the host's prostanoid metabolism  .
In another study, it was found that F. hepatica secretes thioredoxin peroxidase, which recruits and activates macrophages by producing Th2 responses represented by high levels of IL-10 and PGE 2 and low levels of IL-12  .
In 2012, an investigation showed that the Sigma class GST of F. hepatica (FhGST-S1) simulates PG synthase activity promoting the synthesis and release of PGD 2 and PGE 2 from host immune cells, dendritic cells, and macrophages by activation of Th2 cells. The synthesized PGs via FhGST-S1 establishes the infection within the host. PGs are apparently also involved in reproduction by contributing to the development of ova  .
| Concluding remarks|| |
- Although information about the metabolism and function of prostanoids is still scarce, it is obvious that these mediators play a major role in the physiology of parasitic protozoa and helminths.
- These lipids are essential modulators of parasite infectivity and host pathology, irrespective of their source.
- The ability of parasites to synthesize and release prostanoids has obviously become useful and effective in modulating the host response in favor of the parasite.
- Prostanoids are involved in the regulation and interaction between innate and adaptive immunity. The role played by COX metabolites of AA in immunity is complex and may sometimes be contradictory.
- Recently attention has been directed toward the importance of prostanoids and their receptors in modulating adaptive immunity and inflammatory responses.
- Understanding the mechanism by which prostanoids modulate immune response may permit the development of new drug targets selective to each prostanoid receptor. Thus, new drugs for disease management and for inflammatory and immunological disorders may be developed.
| Acknowledgements|| |
Conflicts of interest
There are no conflicts of interest.
| References|| |
Sugimoto Y, Narumiya S, Ichikawa A. Distribution and function of prostanoid receptors: studies from knockout mice. Prog Lipid Res 2000; 39:289-314.
Bergström S, Carlson LA, Weeks JR. The prostaglandins: a family of biologically active lipids. Pharmacol Rev 1968; 20:1-48.
Fleming I. Cytochrome p450 and vascular homeostasis. Circ Res 2001; 89:753-762,
Werz O, Klemm J, Rådmark O, Samuelsson B. p38 MAP kinase mediates stress-induced leukotriene synthesis in a human B-lymphocyte cell line. J Leukoc Biol 2001; 70:830-838.
Noverr MC, Erb-Downward JR, Huffnagle GB. Production of eicosanoids and other oxylipids by pathogenic eukaryotic microbes. Clin Microbiol Rev 2003; 16:517-533.
Tilley SL, Coffman TM, Koller BH. Mixed messages: modulation of inflammation and immune responses by prostaglandins and thromboxanes. J Clin Invest 2001; 108:15-23.
Gualde N, Harizi H. Prostanoids and their receptors that modulate dendritic cell-mediated immunity. Immunol Cell Biol 2004; 82:353-360.
Wang MT, Honn KV, Nie D. Cyclooxygenases, prostanoids, and tumor progression. Cancer Metastasis Rev 2007; 26:525-534.
Legler DF, Bruckner M, Uetz-von Allmen E, Krause P. Prostaglandin E2 at new glance: novel insights in functional diversity offer therapeutic chances. Int J Biochem Cell Biol 2010; 42:198-201.
Kalinski P. Regulation of immune responses by prostaglandin E2. J Immunol 2012; 188:21-28.
Prostanoids-lipidlibrary.aocs.org/Lipids/eicprost/index.htm Updated: May 26th, 2014.
Daugschies A, Joachim A. Eicosanoids in parasites and parasitic infections. Adv Parasitol 2000; 46:181-240.
Noverr MC, Toews GB, Huffnagle GB. Production of prostaglandins and leukotrienes by pathogenic fungi. Infect Immun 2002; 70:400-402.
Ramos S, Custódio A, Silveira H. Anopheles gambiae
eicosanoids modulate Plasmodium berghei
survival from oocyst to salivary gland invasion. Mem Inst Oswaldo Cruz 2014; 109:668-671.
Machado FS, Mukherjee S, Weiss LM, Tanowitz HB, Ashton AW. Bioactive lipids in Trypanosoma cruzi
infection. Adv Parasitol 2011; 76:1-31.
Rouzer CA, Marnett LJ. Non-redundant functions of cyclooxygenases: oxygenation of endocannabinoids. J Biol Chem 2008; 283:8065-8069.
Haeggström JZ, Rinaldo-Matthis A, Wheelock CE, Wetterholm A. Advances in eicosanoid research, novel therapeutic implications. Biochem Biophys Res Commun 2010; 396:135-139.
Santovito D, Mezzetti, A, Cipollone F. Cyclooxygenase and prostaglandin synthases: roles in plaque stability and instability in humans. Curr Opin Lipidol 2009; 20:402-408.
Patrono C, Coller B, FitzGerald GA, Hirsh J, Roth G. Platelet-active drugs: the relationships among dose, effectiveness, and side effects: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004; 126:234S-264S.
Willoughby DA, Moore AR, Colville-Nash PR. Cyclopentenone prostaglandins-new allies in the war on inflammation. Nat Med 2000; 6:137-138.
Tager AM, Luster AD. BLT1 and BLT2: the leukotriene B(4) receptors. Prostaglandins Leukot Essent Fatty Acids 2003; 69:123-134.
Beller TC, Friend DS, Maekawa A, Lam BK, Austen KF, Kanaoka Y. Cysteinyl leukotriene 1 receptor controls the severity of chronic pulmonary inflammation and fibrosis. Proc Natl Acad Sci U S A 2004; 101:3047-3052.
Luster AD, Tager AM. T-cell trafficking in asthma: lipid mediators grease the way. Nat Rev Immunol 2004; 4:711-724.
Pribila JT, Quale AC, Mueller KL, Shimizu Y. Integrins and T cell-mediated immunity. Annu Rev Immunol 2004; 22:157-180.
Liu X, Zhu P, Freedman BD. Multiple eicosanoid-activated nonselective cation channels regulate B-lymphocyte adhesion to integrin ligands. Am J Physiol Cell Physiol 2006; 290:873-882.
Brattig NW, Schwohl A, Rickert R, Büttner DW. The filarial parasite Onchocerca volvulus
generates the lipid mediator prostaglandin E(2). Microbes Infect 2006; 8:873-879.
Wang WEI, Chadee K. Entamoeba histolytica
suppresses gamma interferon-induced macrophage class II major histocompatibility complex Ia molecule and I-A mRNA expression by a prostaglandin E 2-dependent mechanism. Infect Immun 1995; 63:1089-1094.
Sánchez-Ramírez BE, Ramírez-Gil M, Ramos-Martínez E, Rohana PT. Entamoeba histolytica
induces cyclooxygenase-2 expression in macrophages during amebic liver abscess formation. Arch Med Res 2000; 31:122-123.
Stenson WF, Zhang Z, Riehl T, Stanley SL Jr. Amebic infection in the human colon induces cyclooxygenase-2. Infect Immun 2001; 69:3382-3388.
Dey I, Keller K, Belley A, Chadee K. Identification and characterization of a cyclooxygenase-like enzyme from Entamoeba histolytica
. Proc Natl Acad Sci U S A 2003; 100:13561-13566.
Lejeune M, Moreau F, Chadee K. Prostaglandin E2 produced by Entamoeba histolytica
EP4 receptor and alters claudin-4 to increase ion permeability of tight junctions. Am J Pathol 2011; 179:807-818.
Dey I, Chadee K. Prostaglandin E2 produced by Entamoeba histolytica
binds to EP4 receptors and stimulates interleukin-8 production in human colonic cells. Infect Immun 2008; 76:5158-5163.
Barbot L, Topouchian A, Capet C, Magne D, Huneau JF, Kapel N, Gobert JG. Cryptosporidium parvum
: functional study of the intestinal malabsorption syndrome. Ann Pharm Fr 2001; 59:305-311.
Gookin JL, Nordone SK, Argenzio RA. Host responses to Cryptosporidium
infection. J Vet Intern Med 2002;16:12-21.
Jones SL, Blikslager AT. Role of the enteric nervous system in the pathophysiology of secretory diarrhea. J Vet Intern Med 2002; 16:222-228.
Zadrozny LM, Stauffer SH, Armstrong MU, Jones SL, Gookin JL.
Neutrophils do not mediate the pathophysiological sequelae of Cryptosporidium parvum
infection in neonatal piglets. Infect Immun 2006; 74:5497-5505.
Kandil HM, Argenzio RA, Sartor RB. Low endogenous prostaglandin E2 predisposes to relapsing inflammation in experimental rat enterocolitis. Dig Dis Sci 2000; 45:2091-2099.
Cole J, Blikslager A, Hunt E, Gookin J, Argenzio R. Cyclooxygenase blockade and exogenous glutamine enhance sodium absorption in infected bovine ileum. Am J Physiol Gastrointest Liver Physiol 2003; 284:516-524.
Gookin JL, Duckett LL, Armstrong MU, Stauffer SH, Finnegan CP, Murtaugh MP et al
. Nitric oxide synthase stimulates prostaglandin synthesis and barrier function in C. parvum
-infected porcine ileum. Am J Physiol Gastrointest Liver Physiol 2004; 287:571-581.
Gookin JL, Chiang S, Allen J, Armstrong MU, Stauffer SH, Finnegan C, Murtaugh MP. NF-kappaB-mediated expression of iNOS promotes epithelial defense against infection by Cryptosporidium parvum
in neonatal piglets. Am J Physiol Gastrointest Liver Physiol 2006; 290:164-174.
Gookin JL, Foster DM, Coccaro MR, Stauffer SH. Oral delivery of l-arginine stimulates prostaglandin-dependent secretory diarrhea in Cryptosporidium parvum
-infected neonatal piglets. J Pediatr Gastroenterol Nutr 2008; 46:139-146.
Jarroll EL, Muller PJ, Meyer EA, Morse SA. Lipid and carbohydrate metabolism of Giardia lamblia
. Mol Biochem Parasitol 1981; 2:187-196.
Ellis JE, Wyder MA, Jarroll EL, Kaneshiro ES. Changes in lipid composition during in vitro
encystation and fatty acid desaturase activity of Giardia lamblia
. Mol Biochem Parasitol 1996; 81:13-25.
Subramanian AB, Navarro S, Carrasco RA, Marti M, Das S. Role of exogenous inositol and phosphatidylinositol in glycosylphosphatidylinositol anchor synthesis of GP49 by Giardia lamblia
. Biochim Biophys Acta 2000; 1483:69-80.
Das S, Stevens T, Castillo C, Villasenõr A, Arredondo H, Reddy K. Lipid metabolism in mucous-dwelling amitochondriate protozoa. Int J Parasitol 2002; 32:655-675.
Vargas-Villarreal J, Escobedo-Guajardo BL, Mata-Cárdenas BD, Palacios-Corona R, Cortes-Gutiérrez E, Morales-Vallarta M, et al.
Activity of intracellular phospholipase A1 and A2 in Giardia lamblia
. J Parasitol 2007; 93:979-984.
Das S, Castillo C, Stevens T. Phospholipid remodeling/generation in Giardia
: the role of the Lands cycle. Trends Parasitol 2001; 17:316-319.
Morrison HG, McArthur AG, Gillin FD, Aley SB, Adam RD, Olsen GJ, et al
. Genomic minimalism in the early diverging intestinal parasite Giardia lamblia
. Science 2007; 317:1921-1926.
Yichoy M, Nakayasu ES, Shpak M, Aguilar C, Aley SB, Almeida IC, et al
. Lipidomic analysis reveals that phosphatidylglycerol and phosphatidylethanolamine are newly generated phospholipids in an early-divergent protozoan, Giardia lamblia
. Mol Biochem Parasitol 2009; 165:67-78.
Hernandez Y, Castillo C, Roychowdhury S, Hehl A, Aley SB, Das S. Clathrin-dependent pathways and the cytoskeleton network are involved in ceramide endocytosis by a parasitic protozoan, Giardia lamblia
. Int J Parasitol 2007; 37:21-32.
Hernandez Y, Shpak M, Duarte TT, Mendez TL, Maldonado RA, Roychowdhury S, et al
. Novel role of sphingolipid synthesis genes in regulating giardial encystation. Infect Immun 2008; 76:2939-2949.
Sonda S, Stefanic S, Hehl AB. A sphingolipid inhibitor induces a cytokinesis arrest and blocks stage differentiation in Giardia lamblia
. Antimicrob Agents Chemother 2008; 52:563-569.
Stefanic S, Spycher C, Morf L, Casas J, Schraner E, et al.
Inhibition of glucosylceramide synthesis affects cell cycle progression, membrane trafficking and stage differentiation in the minimized protozoan Giardia lamblia
. J Lipid Res 2010; 51:2527-2545.
Shaio MF, Lin PR, Lee CS, Hou SC, Tang P, Yang KD. A novel neutrophil-activating factor released by Trichomonas vaginalis
. Infect Immun 1992; 60:4475-4482.
Sayed el-Ahl SA, el-Wakil HS, Kamel NM, Mahmoud MS. A preliminary study on the relationship between Trichomonas vaginalis
and cervical cancer in Egyptian women. J Egypt Soc Parasitol 2002; 32:167-178.
Tsuji S, Tsujii M, Kawano S, Hori M. Cyclooxygenase-2 upregulation as a perigenetic change in carcinogenesis. J Exp Clin Cancer Res 2001; 20:117-129.
Gupta RA, Tejada LV, Tong BJ, Das SK, Morrow JD, Dey SK, DuBois RN. Cyclooxygenase-1 is overexpressed and promotes angiogenic growth factor production in ovarian cancer. Cancer Res 2003; 63:906-911.
Kulkarni S, Rader JS, Zhang F, Liapis H, Koki AT, Masferrer JL, et al
. Cyclooxygenase-2 is overexpressed in human cervical cancer. Clin Cancer Res 2001; 7:429-434.
Akhtar M, Cheng Y, Magno RM, Ashktorab H, Smoot DT, Meltzer SJ, et al
. Promoter methylation regulates Helicobacter pylori
-stimulated cyclooxygenase-2 expression in gastric epithelial cells. Cancer Res 2001; 61:2399-2403.
Kucknoor A, Mundodi V, Alderete JF. Trichomonas vaginalis
adherence mediates differential gene expression in human vaginal epithelial cells. Cell Microbiol 2005; 7:887-897.
Donders GG, Depuydt CE, Bogers JP, Vereecken AJ. Association of Trichomonas vaginalis
and cytological abnormalities of the cervix in low risk women. PLoS One 2013; 8:e862-e866.
Lazenby GB, Taylor PT, Badman BS, McHaki E, Korte JE, Soper DE, et al
. An association between Trichomonas vaginalis
and high-risk human papillomavirus in rural Tanzanian women undergoing cervical cancer screening. Clin Ther 2014; 36:38-45.
Lonardoni MVC, Barbieri CL, Russo M, Jancar S.
Modulation of Leishmania (L.) amazonensis
growth in cultured mouse macrophages by prostaglandins and platelet-activating factors. Med Inflamm 1994; 3:137-141.
Pérez-Santos JL, Talamás-Rohana P. In vitro
indomethacin administration upregulates interleukin-12 production and polarizes the immune response towards a Th1 type in susceptible BALB/c mice infected with Leishmania mexicana
. Parasite Immunol 2001; 23:599-606.
Matte C, Maion G, Mourad W, Olivier M. Leishmania donovani
-induced macrophages cyclooxygenase-2 and prostaglandin E2 synthesis. Parasite Immunol 2001; 23:177-184.
Ribeiro-Gomes FL, Otero AC, Gomes NA, Moniz-De-Souza MC, Cysne-Finkelstein L, Arnholdt AC, et al
. Macrophage interactions with neutrophils regulate Leishmania major
infection. J Immunol 2004; 172:4454-4462.
Bozza PT, Melo RC, Bandeira-Melo C. Leukocyte lipid bodies regulation and function: contribution to allergy and host defense. Pharmacol Ther 2007; 113:30-49.
Pinheiro RO, Nunes MP, D′Avila H, Bozza PT, Takiya CM, et al.
Induction of autophagy correlates with increased parasite load of Leishmania amazonensis
in BALB/c but not C57BL/6 macrophages. Microbes Infect 2009; 11:181-190.
Guimarães ET, Santos LA, Ribeiro dos Santos R, Teixeira MM, dos Santos WL, Soares MB. Role of interleukin-4 and prostaglandin E2 in Leishmania amazonensis
infection of BALB/c mice. Microbes Infect 2006; 8:1219-1226.
Barreto-de-Souza V, Pacheco GJ, Silva AR, Castro-Faria-Neto HC, Bozza PT, Saraiva EM, et al
. Increased Leishmania
replication in HIV-1-infected macrophages is mediated by tat protein through cyclooxygenase-2 expression and prostaglandin E2 synthesis. J Infect Dis 2006; 194:846-854.
Passero LF, Laurenti MD, Tomokane TY, Corbett CE, Toyama MH. The effect of phospholipase A2 from Crotalus durissus collilineatus
on Leishmania (Leishmania) amazonensis
infection. Parasitol Res 2008; 102:1025-1033.
Bhattacharjee S, Bhattacharjee A, Majumder S, Majumdar SB, Majumdar S. Glycyrrhizic acid suppresses Cox-2-mediated anti-inflammatory responses during Leishmania donovani
infection. J Antimicrob Chemother 2012; 67:1905-1914.
Díaz-Gandarilla JA, Osorio-Trujillo C, Hernández-Ramírez VI, Talamás-Rohana P. PPAR activation induces M1 macrophage polarization via cPLA 2
-COX-2 inhibition, activating ROS production against Leishmania mexicana
. Biomed Res Int 2013; 2013:215283.
Okamoto F, Saeki K, Sumimoto H, Yamasaki S, Yokomizo T. Leukotriene B4 augments and restores Fc gammaRs-dependent phagocytosis in macrophages. J Biol Chem 2010; 285:41113-41121.
Penke LR, Sudan R, Sathishkumar S, Saha B. Prostaglandin E 2
receptors have differential effects on Leishmania major
infection. Parasite immunol 2013; 35:51-54.
von Stebut E, Udey MC. Requirements for Th1-dependent immunity against infection with Leishmania major
. Microbes Infect 2004; 6:1102-1109.
Yong EC, Chi EY, Fritsche TR, Henderson WR Jr. Human platelet-mediated cytotoxicity against Toxoplasma gondii
: role of thromboxane. J Exp Med 1991; 173:65-78.
Yong EC, Chi EY, Henderson WR Jr. Toxoplasma gondii
alters eicosanoid release by human mononuclear phagocytes: role of leukotrienes in interferon gamma-induced antitoxoplasma activity. J Exp Med 1994; 180:1637-1648.
Delemarre FG, Stevenhagen A, Van Furth R. Granulocyte-macrophage colony-stimulating factor (GM-CSF) reduces toxoplasmastatic activity of human monocytes via
induction of prostaglandin E2 (PGE2). Clin Exp Immunol 1995; 102:425-429.
Peng BW, Lin JY, Zhang T. Toxoplasma gondii
induces prostaglandin E2 synthesis in macrophages via signal pathways for calcium-dependent arachidonic acid production and PKC-dependent induction of cyclooxygenase-2. Parasitol Res 2008; 102:1043-1050.
Rangel Moreno J, Estrada García I, De La Luz García Hernández M, Aguilar Leon D, Marquez R. Hernández Pando R The role of prostaglandin E2 in the immunopathogenesis of experimental pulmonary tuberculosis. Immunology 2002; 106:257-266.
Grainger JR, Wohlfert EA, Fuss IJ, Bouladoux N, Askenase MH, Legrand F, et al
. Inflammatory monocytes regulate pathologic responses to commensals during acute gastrointestinal infection. Nat Med 2013; 19:713-721.
Barbosa BF, Paulesu L, Ietta F, Bechi N, Romagnoli R, Gomes AO, et al
. Susceptibility to Toxoplasma gondii
proliferation in BeWo human trophoblast cells is dose-dependent of macrophage migration inhibitory factor (MIF), via ERK1/2 phosphorylation and prostaglandin E2 production. Placenta 2014; 35:152-162.
Gomes AF, Magalhães KG, Rodrigues RM, de Carvalho L, Molinaro R, Bozza PT, et al
. Toxoplasma gondii
-skeletal muscle cells interaction increases lipid droplet biogenesis and positively modulates the production of IL-12, IFN-g and PGE2. Parasit Vectors 2014; 7: 47.
Melo RC, D′Avila H, Fabrino DL, Almeida PE, Bozza PT. Macrophage lipid body induction by Chagas disease in vivo
: putative intracellular domains for eicosanoid formation during infection. Tissue Cell 2003; 35:59-67.
D′Avila H, Freire-de-Lima CG, Roque NR, Teixeira L, Barja-Fidalgo C, Silva AR, et al.
Host cell lipid bodies triggered by Trypanosoma cruzi
infection and enhanced by the uptake of apoptotic cells are associated with prostaglandin E 2
generation and increased parasite growth. J Infect Dis 2011; 204:951-961.
Cardoni RL, Antúnez MI. Circulating levels of cyclooxygenase metabolites in experimental Trypanosoma cruzi
infections. Mediators Inflamm 2004; 13:235-240.
Michelin MA, Silva JS, Cunha FQ. Inducible cyclooxygenase released prostaglandin mediates immunosuppression in acute phase of experimental Trypanosoma cruzi
infection. Exp Parasitol 2005; 111:71-79.
Ashton AW, Mukherjee S, Nagajyothi FN, Huang H, Braunstein VL, Desruisseaux MS, et al
. Thromboxane A2 is a key regulator of pathogenesis during Trypanosoma cruzi
infection. J Exp Med 2007; 204:929-940.
Abdalla GK, Faria GE, Silva KT, Castro EC, Reis MA, Michelin MA Trypanosoma cruzi
: the role of PGE2 in immune response during the acute phase of experimental infection. Exp Parasitol 2008; 118:514-521.
Hideko Tatakihara VL, Cecchini R, Borges CL, Malvezi AD, Graça-de Souza VK, Yamada-Ogatta SF, et al. Effects of cyclooxygenase inhibitors on parasite burden, anemia and oxidative stress in murine Trypanosoma cruzi
infection. FEMS Immunol Med Microbiol 2008; 52:47-58.
Oliveira LG, Kuehn CC, Santos CD, Toldo MP, do Prado JCJr. Enhanced protection by melatonin and meloxicam combination in experimental infection by Trypanosoma cruzi
. Parasite Immunol 2010; 32:245-251.
Rodrigues WF, Miguel CB, Chica JE, Napimoga MH. 15d-PGJ(2) modulates acute immune responses to Trypanosoma cruzi
infection. Mem Inst Oswaldo Cruz 2010; 105:137-143.
Mukherjee S, Machado FS, Huang H, Oz HS, Jelicks LA, Prado CM, et al
. Aspirin treatment of mice infected with Trypanosoma cruzi
and implications for the pathogenesis of Chagas disease. PLoS One 2011; 6: e16959.
Malvezi AD, Da Silva RV, Panis C, et al
. Aspirin modulates innate infl ammatory response and inhibits the entry of Trypanosoma cruzi
in mouse peritoneal macrophages. Mediat Inflamm Mediat Inflamm; 2014, 580919.
Corral RS, Guerrero NA, Cuervo H, Gironès N, Fresno M. Trypanosoma cruzi
infection and endothelin-1 cooperatively activate pathogenic inflammatory pathways in cardiomyocytes. PLoS Negl Trop Dis 2013; 7:e2034.
Machado FS, Mukherjee S, Weiss LM, et al
. Bioactive lipids in Trypanosoma cruzi
infection. In LM Weiss, HB Tanowitz, editors. Advances in parasitology 2011;76:1-31.
Hovsepian E, Mirkin GA, Penas F, et al.
Modulation of inflammatory response and parasitism by 15-Deoxy-Ä(12,14) prostaglandin J(2) in Trypanosoma cruzi
-infected cardiomyocytes. Int J Parasitol 2011; 41:553-562.
Sharma J, Eickhoff CS, Hoft DF, et al.
The absence of myocardial calcium-independent phospholipase A2γ results in impaired prostaglandin E2 production and decreased survival in mice with acute Trypanosoma cruzi
infection. Infect Immun 2013; 81:2278-2287.
Mukherjee S, Sadekar N, Ashton AW, Huang H, Spray DC, Lisanti MP, et al
. Identification of a functional prostanoid-like receptor in the protozoan parasite, Trypanosoma cruzi
. Parasitol Res 2013; 112:1417-1425.
Gomes JA, Molica AM, Keesen TS, Morato MJ, de Araujo FF, Fares RC, et al
. Inflammatory mediators from monocytes down-regulate cellular proliferation and enhance cytokines production in patients with polar clinical forms of Chagas disease. Hum Immunol 2014; 75:20-28.
Bruno B, Kubata K, Duszenko M, et al.
Identificationof a Novel Prostaglandin F 2 Synthase in Trypanosoma brucei
. J Exp Med 2000; 192:1327-1337
Okano Y, Inoue T, Kubata BK, Kabututu Z, Urade Y, Matsumura H, Kai Y.
Crystallization and preliminary X-ray crystallographic studies of Trypanosoma brucei
prostaglandin F(2 alpha) synthase. J Biochem 2002; 132:859-861.
Figarella K, Rawer M, Uzcategui NL, Kubata BK, Lauber K, Madeo F, et al
. Prostaglandin D2 induces programmed cell death in Trypanosoma brucei
bloodstream form. Cell Death Differ 2005; 12:335-346.
Figarella K, Uzcategui NL, Beck A, Schoenfeld C, Kubata BK, Lang F, Duszenko M. Prostaglandin-induced programmed cell death in Trypanosoma brucei
involves oxidative stress. Cell Death Differ 2006; 13:1802-1814.
Perkins DJ, Kremsner PG, Weinberg JB, Inverse relationship of plasma prostaglandin E2 and blood mononuclear cell cyclooxygenase-2 with disease severity in children with Plasmodium falciparum
malaria. J Infect Dis 2001; 183:113-118.
Obata T, Nakano Y, Looareesuwan S, et al.
Prostaglandin spectrum in falciparum
malaria patients. Int Congress Series 2002; 1233:475-478.
Keller CC, Hittner JB, Nti BK, Weinberg JB, Kremsner PG, Perkins DJ. Reduced peripheral PGE2 biosynthesis in Plasmodium falciparum
malaria occurs through hemozoin-induced suppression of blood mononuclear cell cyclooxygenase-2 gene expression via an interleukin-10-independent mechanism. Mol Med 2004; 10:45-54.
Keller CC, Davenport GC, Dickman KR, Hittner JB, Kaplan SS, Weinberg JB, et al
. Suppression of prostaglandin E2 by malaria parasite products and antipyretics promotes overproduction of tumor necrosis factor-alpha: association with the pathogenesis of childhood malarial anemia. J Infect Dis 2006; 193:1384-1393.
Andrade BB, Araújo-Santos T, Luz NF, Khouri R, Bozza MT, Camargo LM, et al
. Heme impairs prostaglandin E2 and TGF-beta production by human mononuclear cells via Cu/Zn superoxide dismutase: insight into the pathogenesis of severe malaria. J Immunol 2010; 185:1196-1204.
Anyona SB, Kempaiah P, Raballah E, Davenport GC, Were T, Konah SN, et al
. Reduced systemic bicyclo-prostaglandin-E2 and cyclooxygenase-2 gene expression are associated with inefficient erythropoiesis and enhanced uptake of monocytic hemozoin in children with severe malarial anemia. Am J Hematol 2012; 87:782-789.
Kuesap J, Na-Bangchang K. Possible role of heme oxygenase-1 and prostaglandins in the pathogenesis of cerebral malaria: heme oxygenase-1 induction by prostaglandin D(2) and metabolite by a human astrocyte cell line. Korean J Parasitol 2010; 48:15-21.
Anyona SB, Kempaiah P, Davenport GC, Vulule JM, Hittner JB, Ong′echa JM, et al
. Suppressed circulating bicyclo-PGE2 levels and leukocyte COX-2 transcripts in children co-infected with P. falciparum
malaria and HIV-1 or bacteremia. Biochem Biophys Res Commun 2013; 436:585-590.
Mpagi JL,Erttmann KD, Brattig NW. The secretory Onchocerca volvulus
protein OvS1/Ov20 exhibits the capacity to compete with serum albumin for the host′s long-chain fatty acids. Mol Biochem Parasitol 2000; 105:273-279.
Sommer A, Rickert R, Fischer P, Steinhart H, Walter RD, Liebau E. A dominant role for extracellular glutathione S-transferase from Onchocerca volvulus
is the production of prostaglandin D2. Infect Immun 2003; 71:3603-3606.
Brattig NW. Pathogenesis and host responses in human onchocerciasis: impact of Onchocerca filariae and Wolbachia endobacteria
[review]. Microbes Infect 2004; 6:113-128.
Perbandt M, Höppner J, Burmeister C, Lüersen K, Betzel C, Liebau E. Structure of the extracellular glutathione S-transferase OvGST1 from the human pathogenic parasite Onchocerca volvulus
. J Mol Biol 2008; 377:501-511.
Brattig NW, Schwohl A, Hoerauf A, Büttner DW. Identification of the lipid mediator prostaglandin E2 in tissue immune cells of humans infected with the filaria Onchocerca volvulus
. Acta Trop 2009; 112:231-235.
Liu LX, Weller PF. Arachidonic acid metabolism in filarial parasites. Exp Parasitol 1990; 71:496-501.
Liu LX, Buhlmann JE, Weller PF. Release of prostaglandin E2 by microfilariae of Wuchereria bancrofti
and Brugia malayi. Am J Trop Med Hyg 1992; 46:520-523.
Morchón R, Roca F, López-Belmonte J, Genchi M, Venco L, Rodríguez-Barbero A, Simón F. Changes in the levels of eicosanoids in cats naturally and experimentally infected with Dirofilaria immitis
. Vet Parasitol 2007; 147:271-275.
Salafsky B, Wang YS, Kevin MB, Hill H, Fusco AC. The role of prostaglandins in cercarial (Schistosoma mansoni
) response to free fatty acids. J Parasitol 1984; 70:584-591.
Tripp CS, Needleman P, Kassab JT, Weinstock JV. Macrophages isolated from liver granulomas of murine Schistosoma mansoni
synthesize predominantly TxA2 during the acute and chronic phases of infection. J Immunol 1988; 140:3140-3143.
Neves SM, Rezende SA, Goes AM. Nitric oxide-mediated immune complex-induced prostaglandin E(2) production by peripheral blood mononuclear cells of humans infected with Schistosoma mansoni
. Cell Immunol 1999; 195:37-42.
Ramaswamy K, Kumar P, He YX. A role for parasite-induced PGE2 in IL-10-mediated host immunoregulation by skin stage schistosomula of Schistosoma mansoni
. J Immunol 2000; 165:4567-4574.
Angeli V, Faveeuw C, Roye O, Fontaine J, Teissier E, Capron A, et al
. Role of the parasite-derived prostaglandin D2 in the inhibition of epidermal Langerhans cell migration during schistosomiasis infection. J Exp Med 2001; 193:1135-1147.
Tang G, Ji M, Wu H, Wu G. Antigen presenting cells may be able to distinguish between normal and radiated Schistosoma japonicum
cercaria: an in vitro
observation. J Biomed Res 2010; 24:285-291.
Zou WL, Yang Z, Zang YJ, Li DJ, Liang ZP, Shen ZY. Inhibitory effects of prostaglandin E1 on activation of hepatic stellate cells in rabbits with schistosomiasis. Hepatobiliary Pancreat Dis Int 2007; 6:176-181.
Thanan R, Murata M, Ma N, Hammam O, Wishahi M, El Leithy T, et al
. Nuclear localization of COX-2 in relation to the expression of stemness markers in urinary bladder cancer. Mediators Inflamm 2012; 2012: 165879.
Sinclair S, Levy G. Eicosanoids and the liver. Int J Gastroenterol 1990; 22:205-213.
Nanji AA, Khwaja S, Sadrzadeh SM. Eicosanoid production in experimental alcoholic liver disease is related to vitamin E levels and lipid peroxidation. Mol Cell Biochem 1994; 140:85-89.
Belley A, Chadee K. Eicosanoid production by parasites: from pathogenesis to immunomodulation? Parasitol Today 1995; 11:327-334.
Ali SF, Joachim A, Daugschies A. Eicosanoid production by adult Fasciola hepatica
and plasma eicosanoid patterns during fasciolosis in sheep. Int J Parasitol 1999; 29:743-748.
Chen L, Daugschies A, Wang B, Mao X. Blood eicosanoids and immune indices during fasciolosis in water buffaloes. Parasitol Int 2000; 49:273-278.
Donnelly S, O′Neill SM, Sekiya M, Mulcahy G, Dalton JP. Thioredoxin peroxidase secreted by Fasciola hepatica
induces the alternative activation of macrophages. Infect Immun 2005; 73:166-173.
LaCourse EJ, Perally S, Morphew RM, Moxon JV, Prescott M, Dowling DJ, et al
. The Sigma class glutathione transferase from the liver fluke Fasciola hepatica
. PLoS Negl Trop Dis 2012; 6:e1666.
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