Prostaglandin D2 inhibits the production of interleukin-12 in murine dendritic cells through multiple signaling pathways.
Prostaglandin (PG) D(2), and its metabolites, are known to be important mediators during acute and chronic inflammation. However, their functions during the early phases of the immune response are poorly documented. In the present study, we show that PGD(2 )inhibits, in a dose-dependent manner, the CD40- and LPS-induced secretion of the Th1-driving factor IL-12 by murine splenic dendritic cells (DC), the most potent antigen-presenting cells. The inhibition of IL-12 production is mediated only in part by the cell surface G alpha s protein-coupled D prostanoid receptor (termed DP1) but not by the G alpha i protein-coupled DP receptor, DP2. We show that recruitment of DP1 in DC results in the activation of a cyclic AMP/protein kinase A pathway that is partially responsible for the inhibition of IL-12 production. We also suggest that the DP1-independent effects exerted by PGD(2) on IL-12 production may be due to the action of ist PGJ(2), but not PGF(2)alpha, metabolites. Electrophoretic mobility shift assays demonstrated that PGD(2) affects NF-kappa B activation through (the) DP1-independent pathway(s). Together these data suggest that PGD(2), by interacting with DP1 and by binding to other target cellular proteins, may regulate immune responses by affecting IL-12 production in DC.
Faveeuw
Christelle
C
Inserm U547, Institut Pasteur de Lille, Lille, France.
Gosset
Philippe
P
Bureau
Fabrice
F
Angeli
Véronique
V
Hirai
Hiroyuki
H
Maruyama
Takayuki
T
Narumiya
Shuh
S
Capron
Monique
M
Trottein
François
F
D000818:Animals; D023201:CD40 Ligand / Q000378:metabolism; D000242:Cyclic AMP / Q000502:physiology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D018664:Interleukin-12 / Q000096:biosynthesis*; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D015230:Prostaglandin D2 / Q000031:analogs & derivatives / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013154:Spleen / Q000276:immunology
C097240:15-deoxy-delta(12,14)-prostaglandin J2; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; D023201:CD40 Ligand; D018664:Interleukin-12; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D015230:Prostaglandin D2; C036293:prostaglandin D2 receptor