Production of TNF-α in Macrophages Activated by T Cells, Compared with Lipopolysaccharide, Uses Distinct IL-10–Dependent Regulatory Mechanism

作者: Gideon Agbanoma , Ching Li , Darren Ennis , Andrew C. Palfreeman , Lynn M. Williams

DOI: 10.4049/JIMMUNOL.1100625

关键词: LipopolysaccharideCell biologySTAT3ImmunologyTranscription (biology)Interleukin 10ChemistryInflammationRheumatoid arthritisEnhancerTumor necrosis factor alpha

摘要: Previously, we demonstrated that spontaneous TNF-α production by macrophages in rheumatoid arthritis (RA) synovial tissue is largely driven contact-dependent activation with T cells tissue. Whereas abundant IL-10 present these RA cultures, it does not adequately control the of TNF-α. In this study, have compared mechanisms involved IL-10–mediated regulation LPS-stimulated stimulated activated cells. We confirm 3′ enhancer region tnf essential for transcription, and its dominated a STAT3-dependent pathway. However, contrast, found transcription or require , subsequently altered clearly mediated dominant STAT3 These observations very important implications our understanding as to how regulates at sites chronic inflammation, such patients RA. Furthermore, distinct will bearing upon identification potential therapeutic targets where stimulus LPS.

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