title: Mechanisms of enhanced macrophage-mediated prostaglandin E2 production and its suppressive role in Th1 activation in Th2-dominant BALB/c mice.
abstract: PGE(2) has been known to suppress Th1 responses. We studied the difference in strains of mice in PGE(2) production by macrophages and its relation to Th1 activation. Macrophages from BALB/c mice produced greater amounts of PGE(2) than those from any other strains of mice, including C57BL/6, after LPS stimulation. In accordance with the amount of PGE(2) produced, macrophage-derived IL-12 and T cell-derived IFN-gamma production were more strongly suppressed in BALB/c macrophages than in C57BL/6 macrophages. When macrophages were treated with indomethacin or EP4 antagonist, Th1 cytokines were more markedly increased in cells from BALB/c mice than in those from C57BL/6 mice. Although cyclooxygenase-2 was expressed similarly after LPS stimulation in these mouse strains, the release of arachidonic acid and the expression of type V secretory phospholipase A(2) mRNA were greater in BALB/c macrophages. However, exogenous addition of arachidonic acid did not reverse the lower production of PGE(2) by C57BL/6 macrophages. The expression of microsomal PGE synthase, a final enzyme of PGE(2) synthesis, was also greater in BALB/c macrophages. These results indicate that the greater production of PGE(2) by macrophages, which is regulated by secretory phospholipase A(2) and microsomal PGE synthase but not by cyclooxygenase-2, is related to the suppression of Th1 cytokine production in BALB/c mice.
authors.affiliation: Department of Immunology, University of Occupational and Environmental Health, School of Medicine, Kitakyushu, Japan. kuroetu@med.uoeh-u.ac.jp
authors.forename: Etsushi
authors.initials: E
authors.lastname: Kuroda
authors.forename: Uki
authors.initials: U
authors.lastname: Yamashita
mesh_terms: D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D019898:Autocrine Communication / Q000276:immunology; D002478:Cells, Cultured; D051546:Cyclooxygenase 2; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D015232:Dinoprostone / Q000096:biosynthesis* / Q000378:metabolism / Q000502:physiology; D005260:Female; D054501:Group II Phospholipases A2; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007527:Isoenzymes / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000276:immunology*; D017737:Macrophages, Peritoneal / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D008805:Mice, Inbred A; D008806:Mice, Inbred AKR; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008811:Mice, Inbred DBA; D019899:Paracrine Communication / Q000276:immunology; D010741:Phospholipases A / Q000096:biosynthesis; D044262:Prostaglandin H2; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis; D011463:Prostaglandins H / Q000378:metabolism; D013045:Species Specificity; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
chemical_list: D016207:Cytokines; D007166:Immunosuppressive Agents; D007527:Isoenzymes; D011463:Prostaglandins H; D016718:Arachidonic Acid; D044262:Prostaglandin H2; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D010741:Phospholipases A; D054501:Group II Phospholipases A2; D015232:Dinoprostone