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

Abstract

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.