Paeoniflorin-6′-o-benzene sulfonate ameliorates the progression of adjuvant-induced arthritis by inhibiting the interaction between Ahr and GRK2 of fibroblast-like synoviocytes

• Published in: International immunopharmacology 2022-07, Vol.108, p.108678-108678, Article 108678
• Main Authors: Zhang, Bing-Jie, Wang, Yue-Ye, Jia, Cheng-Yan, Li, Su-Su, Wang, Xin-Wei, Xu, Yuan, Chen, A-Yuan, Xu, He-Peng, Wang, Chun, Yang, Zhao-Yi, Wei, Wei, Chang, Yan
• Format: Article
• Language: English
• Subjects: Adjuvant-induced arthritis; Aryl hydrocarbon receptor; CP-25; Fibroblasts like synoviocyte; G protein-coupled receptor kinase 2; Rheumatoid arthritis
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2022.108678

[Display omitted] •CP-25 inhibited the development of arthritis.•CP-25 inhibited the development of arthritis in AA rats, which may be related to the inhibition of Ahr expression in synovial tissue.•CP-25 may play an anti-inflammatory immune regulation effect by inhibiting the activation of Ahr and the interaction between Ahr and GRK2 in FLS. Aryl hydrocarbon receptor (Ahr) is thought to be a crucial factor that regulates immune responses, which may be involved in the pathogenesis of autoimmune inflammation including rheumatoid arthritis (RA). The results of our group in recent years have shown that Paeoniflorin-6′-O-benzene sulfonate (code: CP-25), a novel ester derivative of paeoniflorin, has a good effect on improving RA animal models. However, whether the anti-arthritis effect of CP-25 is related to Ahr remains unclear. Here, we showed that CP-25 treatment ameliorated adjuvant-induced arthritis (AA), a rat model of RA, by inhibiting Ahr-related activities in fibroblasts like synoviocytes (FLS). AA rats were treated with CP-25 or paroxetine from days 17 to 33 after immunization. We showed that CP-25 alleviated arthritis symptoms and the pathological changes. Treatment with CP-25 decreased the expression of Ahr in the synovium of AA rats. CP-25 inhibited the expression of Ahr and the G protein-coupled receptor kinase 2 (GRK2) as well as the co-expression of GRK2 with Ahr in FLS of AA rats. Furthermore, CP-25 down-regulated the production of Kyn in FLS of AA rats. These results suggested that CP-25 may inhibit the expression and activation of Ahr. Besides, treatment with CP-25 reduced the proliferation and migration of MH7A caused by Ahr activation. In addition, we also demonstrated that CP-25 down-regulated the total and nuclear expression of Ahr and the expression of GRK2 in Kyn-treated MH7A. Moreover, the co-expression and co-localization of Ahr and GRK2in Kyn-treated MH7A were also repressed by CP-25. The data presented here demonstrated that CP-25 suppressed FLS dysfunction in rats with AA, which were associated with reduced Ahr activation and the interaction between Ahr and GRK2.