Peritoneal Macrophages Release Prostaglandin E and Thromboxane B2 in Response to C3b

ABSTRACT In the present study we investigated the role of platelet-activating factor (PAF) and prostaglandins in experimental Leishmania (Leishmania)amazonensis infection and the relationship between these mediators and nitric oxide (NO) production. Mouse peritoneal macrophages elicited with thioglicolate were infected with leishmania amastigotes, and the infection index determined 48 h later. The course of infection was monitored for 5 weeks in mice infected in the footpad with promastigotes by measuring the footpad swelling and parasite load in regional lymph nodes and spleen. The addition of PAF to C57BL/6 mouse macrophages significantly inhibited parasite growth and induced NO production. Treatment of macrophages with a selective PAF antagonist, WEB2086, increased the infection, indicating that endogenously produced PAF regulates macrophage ability to control leishmania infection. This effect of PAF was abolished by addition of the inhibitor of NO synthesis, L-NAME, to the cultures. The addition of prostaglandin E2 significantly increased the infection and NO production. Treatment with cyclo-oxygenase inhibitor, indomethacin, reduced the infection and PAF-induced release of NO. Thus, the increased NO production induced by PAF seems to be mediated by prostaglandins. The more-selective inhibitors of cyclo-oxygenase 2, nimesulide and NS-398, had no significant effect. Thus, antileishmanial activity correlates better with the presence of PAF or absence of prostaglandins than with NO production. In vivo treatment with PAF antagonists significantly increased leishmania lesions, as well as the parasite load, in regional lymph nodes and spleens. These findings indicate that PAF is essential for the control of leishmania infection.

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Inhibition of Prostaglandin E2 and Leukotriene C4 in Mouse Peritoneal Macrophages and Thromboxane B2 Production in Human Platelets by Flavonoids from Stachys chrysantha and Stachys candida.

Biological and Pharmaceutical Bulletin ◽

10.1248/bpb.23.47 ◽

2000 ◽

Vol 23 (1) ◽

pp. 47-53 ◽

Cited By ~ 36

Author(s):

Helen SKALTSA ◽

Paulina BERMEJO ◽

Diamanto LAZARI ◽

Ana Maria SILVAN ◽

Alexios-Leandros SKALTSOUNIS ◽

...

Keyword(s):

Prostaglandin E2 ◽

Peritoneal Macrophages ◽

Human Platelets ◽

Thromboxane B2 ◽

Leukotriene C4 ◽

Mouse Peritoneal Macrophages

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Aspirin Modulates Innate Inflammatory Response and Inhibits the Entry ofTrypanosoma cruziin Mouse Peritoneal Macrophages

Mediators of Inflammation ◽

10.1155/2014/580919 ◽

2014 ◽

Vol 2014 ◽

pp. 1-9 ◽

Cited By ~ 12

Author(s):

Aparecida Donizette Malvezi ◽

Rosiane Valeriano da Silva ◽

Carolina Panis ◽

Lucy Megumi Yamauchi ◽

Maria Isabel Lovo-Martins ◽

...

Keyword(s):

Inflammatory Response ◽

Chagas Disease ◽

Protozoan Parasite ◽

Inhibitory Effect ◽

Peritoneal Macrophages ◽

Prostaglandin E ◽

Nos Inhibitors ◽

Previously Treated ◽

New Perspective

The intracellular protozoan parasiteTrypanosoma cruzicauses Chagas disease, a serious disorder that affects millions of people in Latin America. Cell invasion byT. cruziand its intracellular replication are essential to the parasite’s life cycle and for the development of Chagas disease. Here, we present evidence suggesting the involvement of the host’s cyclooxygenase (COX) enzyme duringT. cruziinvasion. Pharmacological antagonist for COX-1, aspirin (ASA), caused marked inhibition ofT. cruziinfection when peritoneal macrophages were pretreated with ASA for 30 min at 37°C before inoculation. This inhibition was associated with increased production of IL-1βand nitric oxide (NO∙) by macrophages. The treatment of macrophages with either NOS inhibitors or prostaglandin E2(PGE2) restored the invasive action ofT. cruziin macrophages previously treated with ASA. Lipoxin ALX-receptor antagonist Boc2 reversed the inhibitory effect of ASA on trypomastigote invasion. Our results indicate that PGE2,NO∙, and lipoxins are involved in the regulation of anti-T. cruziactivity by macrophages, providing a better understanding of the role of prostaglandins in innate inflammatory response toT. cruziinfection as well as adding a new perspective to specific immune interventions.

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Faculty Opinions recommendation of Suppression of annexin A2 by prostaglandin E₂ impairs phagocytic ability of peritoneal macrophages in women with endometriosis.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.717993498.793477306 ◽

2013 ◽

Author(s):

Ali Akoum

Keyword(s):

Peritoneal Macrophages ◽

Annexin A2 ◽

Prostaglandin E ◽

Phagocytic Ability

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The Dietary Flavonoid Kaempferol Mediates Anti-Inflammatory Responses via the Src, Syk, IRAK1, and IRAK4 Molecular Targets

Mediators of Inflammation ◽

10.1155/2015/904142 ◽

2015 ◽

Vol 2015 ◽

pp. 1-15 ◽

Cited By ~ 35

Author(s):

Shi Hyoung Kim ◽

Jae Gwang Park ◽

Jongsung Lee ◽

Woo Seok Yang ◽

Gye Won Park ◽

...

Keyword(s):

Inflammatory Responses ◽

Molecular Targets ◽

Peritoneal Macrophages ◽

Cellular Adhesion ◽

Inflammatory Activity ◽

Prostaglandin E ◽

Genes Encoding ◽

Anti Inflammatory

Even though a lot of reports have suggested the anti-inflammatory activity of kaempferol (KF) in macrophages, little is known about its exact anti-inflammatory mode of action and its immunopharmacological target molecules. In this study, we explored anti-inflammatory activity of KF in LPS-treated macrophages. In particular, molecular targets for KF action were identified by using biochemical and molecular biological analyses. KF suppressed the release of nitric oxide (NO) and prostaglandin E2(PGE2), downregulated the cellular adhesion of U937 cells to fibronectin (FN), neutralized the generation of radicals, and diminished mRNA expression levels of inflammatory genes encoding inducible NO synthase (iNOS), TNF-α, and cyclooxygenase- (COX-) 2 in lipopolysaccharide- (LPS-) and sodium nitroprusside- (SNP-) treated RAW264.7 cells and peritoneal macrophages. KF reduced NF-κB (p65 and p50) and AP-1 (c-Jun and c-Fos) levels in the nucleus and their transcriptional activity. Interestingly, it was found that Src, Syk, IRAK1, and IRAK4 responsible for NF-κB and AP-1 activation were identified as the direct molecular targets of KF by kinase enzyme assays and by measuring their phosphorylation patterns. KF was revealed to havein vitroandin vivoanti-inflammatory activity by the direct suppression of Src, Syk, IRAK1, and IRAK4, involved in the activation of NF-κB and AP-1.

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