β-arrestin-2 alleviates rheumatoid arthritis injury by suppressing NLRP3 inflammasome activation and NF-κB pathway in macrophages

Rheumatoid arthritis (RA) is a chronic inflammatory joint disorder that inflicts damage to the joints of the hands and wrist. The aim of this study was to investigate the protective effect of beta-Arrestin-2 (beta Arr2) on RA in vivo and in vitro. The beta Arr2 adenovirus (beta Arr2-Ad) or the control (Con-Ad) was injected into the ankle joint cavity of collagen-induced arthritis (CIA) mice. According to the results, an improvement was shown in the symptoms and pathological injury of RA after an upregulation of beta Arr2. Correspondingly, the inflammatory response was attenuated, as evidenced by the decreased serum pro-inflammatory cytokines levels and NF-kappa B pathway-related proteins. Nucleotide-binding domain leucine-rich repeat and pyrin domain containing receptor 3 (NLRP3) inflammasome activation was inhibited in CIA mice treated with beta Arr2-Ad injection, as reflected by the diminished IL-18 level and declined protein levels of inflammasome components in the ankle joint. Likewise, the anti-inflammatory effect of macrophages was also validated by in vitro experiments. In summary, beta Arr2 effectively ameliorates ankle inflammation in CIA mice via NF-kappa B/NLRP3 inflammasome, providing theoretical and clinical basis for RA therapy.

Automated summary

The study demonstrated that upregulation of beta Arr2 levels can improve symptoms and pathological damage in RA, attenuate inflammatory responses, and effectively alleviate ankle inflammation in CIA mice via the NF-kappa B/NLRP3 inflammasome pathway.