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• W1925686064 abstract "Abstract Allergic contact dermatitis, caused by metallic ions, is a T cell-mediated inflammatory skin disease. IL-12 is a 70-kDa heterodimeric protein composed of IL-12p40 and IL-12p35, playing a major role in the generation of allergen-specific T cell responses. Dendritic cells (DCs) are APCs involved in the induction of primary immune responses, as they possess the ability to stimulate naive T cells. In this study, we address the question whether the sensitizer nickel sulfate (NiSO4) itself or in synergy with other signals can induce the secretion of IL-12p70 in human monocyte-derived DCs (Mo-DCs). We found that IL-12p40 was produced by Mo-DC in response to NiSO4 stimulation. Addition of IFN-γ concomitantly to NiSO4 leads to IL-12p70 synthesis. NiSO4 treatment leads to the activation of MAPK, NF-κB pathways, and IFN regulatory factor 1 (IRF-1). We investigated the role of these signaling pathways in IL-12 production using known pharmacological inhibitors of MAPK and NF-κB pathways and RNA interference-mediated silencing of IRF-1. Our results showed that p38 MAPK, NF-κB, and IRF-1 were involved in IL-12p40 production induced by NiSO4. Moreover, IRF-1 silencing nearly totally abrogated IL-12p40 and IL-12p70 production provoked by NiSO4 and IFN-γ. In response to NiSO4, we observed that STAT-1 was phosphorylated on both serine and tyrosine residues and participated to NiSO4-induced IRF-1 activation. N-acetylcysteine abolished STAT-1 phosphorylation, suggesting that STAT-1 activation may be dependent on NiSO4-induced alteration of the redox status of the cell. These results indicate that p38 MAPK, NF-κB, and IRF-1 are activated by NiSO4 in Mo-DC and cooperate for IL-12 production." @default.
• W1925686064 created "2016-06-24" @default.
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• W1925686064 date "2010-07-01" @default.
• W1925686064 modified "2023-09-27" @default.
• W1925686064 title "Mechanisms of IL-12 Synthesis by Human Dendritic Cells Treated with the Chemical Sensitizer NiSO4" @default.
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• W1925686064 doi "https://doi.org/10.4049/jimmunol.0901992" @default.
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