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- W4313354613 abstract "Abstract The proinflammatory cytokine IL-23 emerged recently as a key player in autoimmune diseases. Production of IL-23 by pathogen-activated dendritic cells (DC) is regulated by endogenous mediators such as prostaglandin E2 (PGE2) and interferon-γ (IFN-γ). PGE2 stimulates IL-23 and inhibits IL-12 production. In contrast, IFN-γ inhibits IL-23 and stimulates IL-12. In the presence of both PGE2 and IFN-γ, TLR-stimulated DC produce higher levels of both cytokines. Here we analyze the signaling pathways involved in this complex regulation. IRF1, induced by LPS and at high levels by IFN-γ, acts as a positive transcription factor for IL-12p40, and as a negative regulator for IL-23p19. The potent effect of IFN-γ on IRF1 correlates with the inhibition of IL-23 and stimulation of IL-12 in LPS-activated DC. In contrast, PGE2 abolishes IRF1 expression in LPS-stimulated DC, resulting in the inhibition of IL-12 and stimulation of IL-23 production. When both PGE2 and IFN-γ are present, the IRF1 levels are similar to LPS controls, allowing for both IL-23p19 and IL-12p40 expression. In addition, as previously reported by us, the stimulatory effect of PGE2 on p19 transcription is also mediated through the activation of the positive transcription factors CREB and C/EBP. Our findings suggest that the combined presence of PGE2 and IFN-γ in autoimmune conditions results in sustained production of both IL-12 and IL-23, which contribute to the maintenance of a proinflammatory environment." @default.
- W4313354613 created "2023-01-06" @default.
- W4313354613 creator A5009635192 @default.
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- W4313354613 creator A5059699591 @default.
- W4313354613 date "2013-05-01" @default.
- W4313354613 modified "2023-09-27" @default.
- W4313354613 title "PGE2 modulates the ability of IFN-γ to inhibit IL-23 production in activated dendritic cells (P6333)" @default.
- W4313354613 doi "https://doi.org/10.4049/jimmunol.190.supp.184.28" @default.
- W4313354613 hasPublicationYear "2013" @default.
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