Pharmacologic Repression of Retinoic Acid Receptor-Related Orphan Nuclear Receptor gamma Is Therapeutic in the Collagen-Induced Arthritis Experimental Model

摘要

Objective. The nuclear receptor retinoic acid receptor-related orphan nuclear receptor gamma (ROR gamma; T cell-specific isoform ROR gamma t) is a key regulator of Th17 cell differentiation, controlling the production of the inflammatory cytokine interleukin-17 (IL-17). Lipopolysaccharide (LPS) stimulation of monocytes leads to the induction of ROR gamma. We previously showed that the potent and selective inverse agonist of ROR gamma, SR2211, was effective at suppressing IL-17 production in EL4 cells. The aim of this study was to examine the effects of SR2211 treatment on proinflammatory cytokine expression in LPS-stimulated RAW 264.7 cells as well as on joint inflammation in vivo in mice with collagen-induced arthritis (CIA).