Prostaglandin E2 up-regulates macrophage-derived chemokine production but suppresses IFN-inducible protein-10 production by APC.
PGE(2) has been known to suppress Th1 responses. We studied the role of PGE(2) in two representative chemokines, macrophage-derived chemokine (MDC) and IFN-inducible protein-10, production by LPS- or CD40-stimulated spleen cells. The production of MDC, one of the ligands for CCR4 preferentially expressed on Th2, was enhanced in nonstimulated, LPS-, CD40-, or CD3-stimulated spleen cells by the pretreatment with PGE(2), while the production of IFN-inducible protein-10, a representative ligand for CXC chemokine receptor 3 expressed on Th1, was suppressed. MDC production was also enhanced by IL-4, IL-5, and intracellular cAMP-elevating agents such as dibutyryl cAMP and 3-isobutyl-1-methylxanthine, and the effect of IL-4, IL-5, and PGE(2) was additive. However, the pretreatment with IL-6, IL-10, or TGF-beta, or the neutralization of IFN-gamma or IL-12 had no effect on MDC production. B cells, macrophages, and dendritic cells were main producers of MDC, while T cells produced only a small amount of MDC. MDC production by B cells was equally stimulated by LPS and anti-CD40 Ab, while that by macrophages and dendritic cells was more markedly stimulated by anti-CD40 Ab, and PGE(2) further enhanced MDC production by these stimulated cells. These results indicate that PGE(2) regulates Th1/Th2-related chemokine production by B cells, macrophages, and dendritic cells, and that this is a new function of PGE(2) for the regulation of Th2 immune responses at the induction and activation stages.
Kuroda
E
E
Department of Immunology, University of Occupational and Environmental Health, School of Medicine, Kitakyushu, Japan.
Sugiura
T
T
Okada
K
K
Zeki
K
K
Yamashita
U
U
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D001402:B-Lymphocytes / Q000276:immunology; D019013:CD40 Antigens / Q000276:immunology; D002478:Cells, Cultured; D054422:Chemokine CCL22; D054357:Chemokine CXCL10; D019742:Chemokines, CC / Q000096:biosynthesis*; D019743:Chemokines, CXC / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D000242:Cyclic AMP / Q000378:metabolism; D016207:Cytokines / Q000494:pharmacology; D003713:Dendritic Cells / Q000276:immunology; D015232:Dinoprostone / Q000494:pharmacology* / Q000502:physiology; D015536:Down-Regulation / Q000187:drug effects / Q000276:immunology*; D007106:Immune Sera / Q000494:pharmacology; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology*; D007424:Intracellular Fluid / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation; D008264:Macrophages / Q000276:immunology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology*
D000276:Adjuvants, Immunologic; D019013:CD40 Antigens; C515483:Ccl22 protein, mouse; D054422:Chemokine CCL22; D054357:Chemokine CXCL10; D019742:Chemokines, CC; D019743:Chemokines, CXC; D016207:Cytokines; D007106:Immune Sera; D007166:Immunosuppressive Agents; D008070:Lipopolysaccharides; D007371:Interferon-gamma; D000242:Cyclic AMP; D015232:Dinoprostone