Electroacupuncture Ameliorate Juvenile Collagen-Induced Arthritis by Regulating M1 Macrophages and Pyroptosis Signaling Pathways

Abstract

Background: Electroacupuncture (EA) exerts significant effects in clinic, such as anti-inflammation, immune regulation, joint-related diseases, anti-cancer, etc. However, the mechanism by which EA protects juvenile idiopathic arthritis (JIA) is obscure. Thus, we explored the protective mechanisms in the juvenile collagen-induced arthritis (CIA) rat model deeply and investigated the effect of EA against synovial inflammation and whether this effect depends on the regulation of macrophage polarization.Methods: Sprague-Dawley (SD) rats (3–4 weeks) were used to establish the collagen-induced arthritis (CIA) model. The CIA rats received EA treatment once a day from day 21 of modeling, with the treatment lasting for four weeks. The anti-arthritic and anti-inflammatory effects of EA were studied using arthritis score, Immunostaining, Quantitative real-time PCR (qPCR), Western blotting (WB) and enzyme-linked immunosorbent assay (ELISA). The related pro/anti-inflammatory cytokines were detected by ELISA, qPCR, and WB. Western blotting was used to investigate the effect of EA on NLRP3, GSDMD, and Caspase-1 in the joint synovial tissues.Results: We found that EA inhibited joint inflammation, cartilage damage, and bone destruction in CIA rats. EA effectively alleviated the high expression of inflammatory cytokines in synovial tissue in vivo. EA treatment shifted macrophages from the M1 phenotype to the M2 phenotype. The expression of inducible nitric oxide synthase (iNOS) and other proinflammatory cytokines released by M1 macrophages was decreased in the EA group. However, simultaneously, the expression of markers of anti-inflammatory M2 macrophages, such as arginase (Arg)-1 and interleukin (IL)-10, was increased. In addition, EA treatment attenuated pyroptosis by downregulating the expression of NLRP3, GDSMD, and caspase-1, thereby preventing inflammatory cell death resulting from the release of IL-1β and IL-18.Conclusion: EA can effectively improve joints inflammation of juvenile collagen-induced arthritis rats by inhibiting M1 phenotype polarization and pyroptosis pathway in the joint synovial tissues.