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• W2577112812 endingPage "1530" @default.
• W2577112812 startingPage "1521" @default.
• W2577112812 abstract "IL-27, a multifunctional cytokine produced by APCs, antagonizes inflammation by affecting conventional dendritic cells (cDC), inducing IL-10, and promoting development of regulatory Tr1 cells. Although the mechanisms involved in IL-27 induction are well studied, much less is known about the factors that negatively impact IL-27 expression. PGE2, a major immunomodulatory prostanoid, acts as a proinflammatory agent in several models of inflammatory/autoimmune disease, promoting primarily Th17 development and function. In this study, we report on a novel mechanism that promotes the proinflammatory function of PGE2 We showed previously that PGE2 inhibits IL-27 production in murine bone marrow-derived DCs. In this study, we show that, in addition to bone marrow-derived DCs, PGE2 inhibits IL-27 production in macrophages and in splenic cDC, and we identify a novel pathway consisting of signaling through EP2/EP4→induction of cAMP→downregulation of IFN regulatory factor 1 expression and binding to the p28 IFN-stimulated response element site. The inhibitory effect of PGE2 on p28 and irf1 expression does not involve endogenous IFN-β, STAT1, or STAT2, and inhibition of IL-27 does not appear to be mediated through PKA, exchange protein activated by cAMP, PI3K, or MAPKs. We observed similar inhibition of il27p28 expression in vivo in splenic DC following administration of dimethyl PGE2 in conjunction with LPS. Based on the anti-inflammatory role of IL-27 in cDC and through the generation of Tr1 cells, we propose that the PGE2-induced inhibition of IL-27 in activated cDC represents an important additional mechanism for its in vivo proinflammatory functions." @default.
• W2577112812 created "2017-01-26" @default.
• W2577112812 creator A5020844761 @default.
• W2577112812 creator A5027884950 @default.
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• W2577112812 creator A5088349580 @default.
• W2577112812 date "2017-01-06" @default.
• W2577112812 modified "2023-10-15" @default.
• W2577112812 title "Prostaglandin E₂Inhibition of IL-27 Production in Murine Dendritic Cells: A Novel Mechanism That Involves IRF1" @default.
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• W2577112812 doi "https://doi.org/10.4049/jimmunol.1601073" @default.
• W2577112812 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5296337" @default.
• W2577112812 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/28062696" @default.
• W2577112812 hasPublicationYear "2017" @default.

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