IL-1 beta induces dendritic cells to produce IL-12.
The cytokine IL-12, a product of dendritic cells (DC), plays a major role in cellular immunity, notably by inducing lymphocytes to produce IFN-gamma. Microbial products, T cell signals and cytokines induce the production of IL-12. Here, IL-1 beta is identified as a new IL-12-inducing agent, acting conjointly with CD40 ligand (CD40L) on human monocyte-derived DC in vitro. The effects of IL-1 beta were dose dependent, specifically blocked by neutralizing antibodies, and were observed both in immature and mature DC. Immature DC secreted more IL-12 than mature DC, but the effects of IL-1 beta were not due to a block of DC maturation as determined by analysis of DC surface markers. The mechanisms of action of IL-1 beta could be contrasted to that of other inducers of IL-12 such as IFN-gamma and lipopolysaccharide (LPS). Either IL-1 beta or IFN-gamma co-induced IL-12 with CD40L but conjointly, IL-1 beta, CD40L and IFN-gamma synergized, inducing very high levels of IL-12. The effects of IL-1 beta differed from those of LPS in that IL-1 beta, unlike LPS, could not induce IL-12 solely after IFN-gamma priming; and when combined with CD40L, IL-1 beta, unlike LPS, induced little IL-10. The mechanism of action of IL-1 beta involves IL-12 alpha mRNA up-regulation, and we show that the combination of CD40L and IL-1 beta induces high levels of IL-12 alpha and IL-12 beta mRNA in DC. Altogether, these results delineate a new mechanism linking adaptive and innate immune responses for the regulation of IL-12 production in DC and for the role of IL-1 beta in the development of cellular immunity.
Wesa
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Barbara Ann Karmanos Cancer Institute of Wayne State University, Detroit, MI 48201, USA.
Galy
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A
D019138:Antibodies, Blocking; D000918:Antibody Specificity; D023201:CD40 Ligand / Q000494:pharmacology; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D019281:Dimerization; D004306:Dose-Response Relationship, Immunologic; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D007106:Immune Sera / Q000494:pharmacology; D007371:Interferon-gamma / Q000276:immunology; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000276:immunology / Q000494:pharmacology*; D018664:Interleukin-12 / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology
D019138:Antibodies, Blocking; D007106:Immune Sera; D007375:Interleukin-1; D008070:Lipopolysaccharides; D023201:CD40 Ligand; D018664:Interleukin-12; D007371:Interferon-gamma