SIRT1 inhibits differentiation of monocytes to macrophages: amelioration of synovial inflammation in rheumatoid arthritis

摘要: Monocyte-to-macrophage differentiation plays a central role in the pathophysiology of rheumatoid arthritis (RA)-associated inflammation because it results secretions various inflammatory mediators inflamed synovium, and thus, this is viewed as clinical target. We aimed to determine whether SIRT1 inhibits monocytes from RA patients into macrophages by suppressing PU.1 phosphorylation. Monocytes synovial fluid (RAMCs), THP-1 monocytes, mouse bone marrow-derived (BMDCs) were studied. The phorbol 12-myristate 13-acetate (PMA)-stimulated monocyte adherence was significantly inhibited resveratrol (a activator), inhibition prevented pretreating cells with sirtinol inhibitor). Furthermore, pretreatment PMA-induced expressions macrophage surface markers (CD11b, CD14, CD36) NF-κB transcriptional activation and, suppressed proinflammatory cytokines (TNF-α, IL-1β, IL-6). In transgenic (Tg) mice, activity TNF-α, IL-6 decreased at protein mRNA levels versus control C57BL/6 mice. phosphorylation nuclear translocation differentiation. conclusion, appears inhibit signaling, which suggests critical regulation RA.