Pharmacological repression of RORγ is therapeutic in the collagen-induced arthritis experimental model

摘要

ObjectiveThe nuclear receptor RORγ (RAR-related orphan receptor gamma; T cell specific isoform is RORγt) is a key regulator of TH17 cell differentiation controlling the production of the inflammatory cytokine IL17. Further it has been shown that LPS stimulation of monocytes leads to induction of RORγ. Previously we have shown that the potent and selective inverse agonist of RORγ, SR2211 was effective at suppressing IL17 production in EL4 cells. Further we demonstrate here that SR2211 treatment blocks proinflammatory cytokine expression in LPS stimulated RAW264.7 cells. Based on these findings SR2211 was administered to collagen-induced arthritis (CIA) mice to evaluate the ability of the compound to reduce joint inflammation.