Inhibition of NEMO alleviates arthritis by blocking the M1 macrophage polarization.

Abstract

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.