title: Sensitivity difference to the suppressive effect of prostaglandin E2 among mouse strains: a possible mechanism to polarize Th2 type response in BALB/c mice.
abstract: PGE2 has been shown to play a prominent role in regulating Th1 and Th2 type responses. We studied the role of PGE2 in IFN-gamma production by Staphylococcus aureus Cowan I-stimulated spleen cells from several mouse strains such as BALB/c, C3H/HeN, and C57BL/6. When spleen cells were pretreated with indomethacin (cyclooxygenase (COX)-1 and COX-2 inhibitor) or NS-398 (COX-2-specific inhibitor), S. aureus Cowan I -induced IFN-gamma production was increased more markedly in spleen cells from BALB/c mice than from C3H/HeN and C57BL/6 mouse. However, PGE2 production was not significantly different among spleen cells from three mouse strains. When various concentrations of PGE2 were exogeneously added to spleen cells, PGE2 showed a stronger suppressive effect on IFN-gamma production in spleen cells from BALB/c mice than from other strains of mice. This suppressive effect of PGE2 in BALB/c mice mainly depended on IL-12p70 production by APCs. More PGE2 binding sites were found in BALB/c spleen cells than in C3H/HeN spleen cells, indicating that the sensitivity difference to the suppressive effect of PGE2 was due to the difference of the number of PGE2 receptors. The administration of NS-398 into BALB/c mice enhanced Ag-specific IFN-gamma production, but not IL-4 production. This effect is the same as IL-12 administration in vivo. From these results, we propose that the modulation of PGE2 is important for Th1 activation via IFN-gamma and IL-12p70 production in vitro and in vivo and that PGE2 is one of the pivotal factors in the Th2-dominant immune response in BALB/c mice.
authors.affiliation: Department of Immunology, University of Occupational and Environmental Health, School of Medicine, Kitakyushu, Japan.
authors.forename: E
authors.initials: E
authors.lastname: Kuroda
authors.forename: T
authors.initials: T
authors.lastname: Sugiura
authors.forename: K
authors.initials: K
authors.lastname: Zeki
authors.forename: Y
authors.initials: Y
authors.lastname: Yoshida
authors.forename: U
authors.initials: U
authors.lastname: Yamashita
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D001665:Binding Sites / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D051546:Cyclooxygenase 2; D016207:Cytokines / Q000502:physiology; D015232:Dinoprostone / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D007111:Immunity, Cellular / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D007273:Injections, Intramuscular; D007274:Injections, Intraperitoneal; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D016753:Interleukin-10 / Q000494:pharmacology; D007527:Isoenzymes / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C / Q000276:immunology*; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000502:physiology; D009578:Nitrobenzenes / Q000008:administration & dosage; D011451:Prostaglandin-Endoperoxide Synthases / Q000494:pharmacology; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D013449:Sulfonamides / Q000008:administration & dosage; D018417:Th1 Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism
chemical_list: D000276:Adjuvants, Immunologic; D016207:Cytokines; D007166:Immunosuppressive Agents; D007527:Isoenzymes; D009578:Nitrobenzenes; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D016753:Interleukin-10; D009569:Nitric Oxide; D007371:Interferon-gamma; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone