Medermycin Inhibits TNFα-Promoted Inflammatory Reaction in Human Synovial Fibroblasts

International Journal of Molecular Sciences(2023)

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摘要
Synovial inflammation plays a crucial role in the destruction of joints and the experience of pain in osteoarthritis (OA). Emerging evidence suggests that certain antibiotic agents and their derivatives possess anti-inflammatory properties. Medermycin (MED) has been identified as a potent antibiotic, specifically active against Gram-positive bacteria. In this study, we aimed to investigate the impact of MED on TNFα-induced inflammatory reactions in a synovial cell line, SW-982, as well as primary human synovial fibroblasts (HSF) using RNA sequencing, rtRT-PCR, ELISA, and western blotting. Through the analysis of differentially expressed genes (DEGs), we identified a total of 1478 significantly upregulated genes in SW-982 cells stimulated with TNFα compared to the vehicle control. Among these upregulated genes, MED treatment led to a reduction in 1167 genes, including those encoding proinflammatory cytokines such as IL1B, IL6, and IL8. Pathway analysis revealed the enrichment of DEGs in the TNF and NFκB signaling pathway, further supporting the involvement of MED in modulating inflammatory responses. Subsequent experiments demonstrated that MED inhibited the expression of IL6 and IL8 at both the mRNA and protein levels in both SW982 cells and HSF. Additionally, MED treatment resulted in a reduction in p65 phosphorylation in both cell types, indicating its inhibitory effect on NFκB activation. Interestingly, MED also inhibited Akt phosphorylation in SW982 cells, but not in HSF. Overall, our findings suggest that MED suppresses TNFα-mediated inflammatory cytokine production and p65 phosphorylation. These results highlight the potential therapeutic value of MED in managing inflammatory conditions in OA. Further investigations utilizing articular chondrocytes and animal models of OA may provide valuable insights into the therapeutic potential of MED for this disease.
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关键词
human synovial fibroblasts,inflammatory reaction
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