Moxibustion regulates the polarization of macrophages through the STAT1/miR-155/SOCS1 pathway in rheumatoid arthritis

Abstract Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent synovitis. Moxibustion is a natural therapy that exhibits anti-inflammatory bioactivity. However, the mechanism of moxibustion in the treatment of RA still needs further study. Objective: This study aimed to observe the effects of moxibustion on macrophage polarization and the STAT1/miR-155/SOCS1 signaling pathway in rats with RA. Methods: The rats' right hind paws were injected with freundʼs complete adjuvant (FCA) to establish the model of RA. Seven days post-FCA injection, moxibustion therapy was performed on the acupoints of Shenshu (BL23) and Zusanli (ST36) once a day for three weeks. The thickness of the foot pad, histopathological changes and inflammatory cytokines were then analyzed. The Immunofluorescence and Elisa were employed to evaluate the impact of moxibustion on the expression of macrophage's markers and the expression of molecules related to the STAT1/miR-155/SOCS1 signaling pathway. Results: Following the injection of FCA, it was observed that the thickness of the foot pad increased, the joint space narrowed, and a significant number of inflammatory cells infiltrated the area. However, after the moxibustion treatment, these symptoms were improved. Additionally, the levels of IL-23 were down-regulated, while the levels of IL-4, IL-10, and Arginase (Arg)-1 were up-regulated. The polarization balance of macrophages in the RA rats was disrupted, with a stronger polarization towards M1 and a weaker polarization towards M2. Post-moxibustion treatment, the polarization of macrophages was corrected, characterized by an increase in M2-polarized macrophages and a decrease in M1-polarized macrophages. Furthermore, moxibustion inhibited the expression of STAT1 and miR-155 within the STAT1/miR-155/SOCS1 pathway and promoted the expression of SOCS1, which was conducive to regulating the polarization phenotype of macrophages. Conclusion: The results demonstrated that moxibustion regulated the polarization phenotype of macrophages and exhibited anti-inflammatory effects, which may be related to the regulation of macrophage polarization through the STAT1/miR-155/SOCS1 pathway.