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• W1544335514 endingPage "6366" @default.
• W1544335514 startingPage "6358" @default.
• W1544335514 abstract "The murine calcium binding protein S100A8 (A8) is a leukocyte chemoattractant, but high levels may be protective and scavenge hypochlorite. A8 is induced by LPS, IFN-gamma, and TNF in elicited macrophages. Th2 cytokines generally suppress proinflammatory gene expression, and IL-4 and IL-13 partially decreased A8 induction in macrophages and endothelial cells stimulated by LPS or IFN. In contrast, IL-10 synergized with LPS and IFN to increase mRNA levels > or =9-fold and secreted A8 levels approximately 4-fold. IL-10 decreased the optimal time of mRNA expression induced by LPS from 24 to 8 h. Blocking experiments indicated that endogenous IL-10 contributes to gene induction by LPS. Cooperation between IL-10 and LPS was not due to altered mRNA stability but was dependent on de novo protein synthesis. Transfection analysis with A8 luciferase constructs confirmed that synergy was due to increased transcription. The region of the promoter involved was localized to a 178-bp fragment flanking the transcription start site of the gene. This region was also responsible for the suppressive effects of IL-4 and IL-13. Forskolin, CTP-cAMP, and PGE(2) also enhanced LPS- and IFN-induced A8 mRNA, whereas indomethacin significantly reduced synergy between IL-10 and LPS. Mitogen-activated protein kinase/cyclooxygenase 2/cAMP pathways involving CCAAT-enhancing binding protein, located within the active promoter, may mediate A8 gene up-regulation in a manner mechanistically distinct to genes regulated by IL-10 via the STAT pathway. A8 exhibits pleiotropic effects, and the high levels secreted as a result of IL-10 synergy may regulate untoward inflammatory damage by virtue of its an antioxidant capacity." @default.
• W1544335514 created "2016-06-24" @default.
• W1544335514 creator A5024247143 @default.
• W1544335514 creator A5058220968 @default.
• W1544335514 creator A5077154137 @default.
• W1544335514 date "2001-05-15" @default.
• W1544335514 modified "2023-09-25" @default.
• W1544335514 title "IL-10 Up-Regulates Macrophage Expression of the S100 Protein S100A8" @default.
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• W1544335514 doi "https://doi.org/10.4049/jimmunol.166.10.6358" @default.
• W1544335514 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/11342660" @default.
• W1544335514 hasPublicationYear "2001" @default.
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