CCR2 antagonist represses fibroblast-like synoviocyte-mediated inflammation in patients with rheumatoid arthritis.

Rheumatoid arthritis (RA) is a common autoimmune disease with a global incidence of approximately 1%. Its complex pathogenesis makes the development of RA-related therapeutics very difficult. Existing drugs for RA have many side effects and are prone to drug resistance. One potential target for RA drugs includes C-Cchemokinereceptortype2 (CCR2), which belongs to the G protein-coupled receptor family. A series of RA drugs targeting CCR2 have been developed; however, the pre-clinical and clinical research results for CCR2 antagonists are inconsistent. We found that CCR2 was also expressed in primary Fibroblast-like synoviocyte (FLS) from patients with RA. CCR2 antagonists can inhibit inflammatory cytokines and matrix metalloproteinases released by RA-FLS but do not affect the proliferation and migration ability of RA-FLS. In addition, CCR2 antagonist-treated RA-FLS indirectly repressed macrophage-mediated inflammation and rescued the viability of chondrocytes. Finally, a CCR2 antagonist ameliorated the collagen-induced arthritic (CIA). CCR2 antagonists may exert anti-inflammatory effects on RA-FLS by inhibiting the JAK-STAT pathway. In summary, a CCR2 antagonist can exert anti-inflammatory effects by acting on RA-FLS. This study provides a new experimental basis for the use of CCR2 antagonists in the development of RA drugs.

Informations de copyright

Copyright © 2023 Elsevier B.V. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.