Han Xiao, Li Qing, Zhang Shumin, Sun Linqian, Liu Wenping, Wang Jibo
Department of Rheumatology & Clinical Immunology, The Affiliated Hospital of Qingdao University, PR China.
Department of Rheumatology & Clinical Immunology, The Affiliated Hospital of Qingdao University, PR China.
Int Immunopharmacol. 2023 Apr;117:109983. doi: 10.1016/j.intimp.2023.109983. Epub 2023 Mar 10.
The nuclear factor-kappa B (NF-κB) signaling pathway and macrophages are critically involved in the pathogenesis of rheumatoid arthritis (RA). Recent studies have identified NF-κB essential modulator (NEMO), a regulatory subunit of the inhibitor of NF-κB kinase (IKK), as a potential target to inhibit NF-κB signaling pathway. Here, we investigated the interactions between NEMO and M1 macrophage polarization in RA. NEMO inhibition led to the suppression of proinflammatory cytokines secreted from M1 macrophages in collagen-induced arthritis mice. From lipopolysaccharide (LPS)-stimulated RAW264, knocking down NEMO blocked M1 macrophage polarization accompanied by lesser M1 proinflammatory subtype. Our findings link the novel regulatory component of NF-κB signaling and human arthritis pathologies which will pave the way towards the identification of new therapeutic targets and the development of innovative preventive strategies.
核因子-κB（NF-κB）信号通路和巨噬细胞在类风湿性关节炎（RA）的发病机制中起着关键作用。最近的研究已确定NF-κB必需调节因子（NEMO），即NF-κB激酶（IKK）抑制剂的一个调节亚基，是抑制NF-κB信号通路的一个潜在靶点。在此，我们研究了RA中NEMO与M1巨噬细胞极化之间的相互作用。在胶原诱导的关节炎小鼠中，NEMO抑制导致M1巨噬细胞分泌的促炎细胞因子受到抑制。从脂多糖（LPS）刺激的RAW264中敲低NEMO可阻断M1巨噬细胞极化，同时M1促炎亚型减少。我们的研究结果将NF-κB信号的新型调节成分与人类关节炎病理联系起来，这将为确定新的治疗靶点和开发创新的预防策略铺平道路。
