HIF1α inhibition facilitates Leflunomide-AHR-CRP signaling to attenuate bone erosion in CRP-aberrant rheumatoid arthritis.

ABSTRACT: Rheumatoid arthritis (RA) is a chronic inflammatory disorder characterized by progressive bone erosion. Leflunomide is originally developed to suppress inflammation via its metabolite A77 1726 to attenuate bone erosion. However, distinctive responsiveness to Leflunomide is observed among RA individuals. Here we show that Leflunomide exerts immunosuppression but limited efficacy in RA individuals distinguished by higher serum C-reactive protein (CRP^Higher, CRP^H), whereas the others with satisfactory responsiveness to Leflunomide show lower CRP (CRP^Lower, CRP^L). CRP inhibition decreases bone erosion in arthritic rats. Besides the immunomodulation via A77 1726, Leflunomide itself induces AHR-ARNT interaction to inhibit hepatic CRP production and att

SUBMITTER: Liang C 

PROVIDER: S-EPMC6783548 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature