Rheumatoid arthritis (RA) is a chronic autoimmune disease with high morbidity and mortality. Within the inflammatory milieu, resident fibroblast-like synoviocytes (FLS) in the synovial tissue undergo hyperplasia, which leads to joint destruction. Research suggests that activation of the aryl hydrocarbon receptor (AHR) pathway plays an instrumental role in the inflammatory and destructive RA phenotype. Treatment with AHR antagonist GNF351 [N-[2-(3H-indol-3-yl)ethyl]-9-isopropyl-2-(5-methyl-3-pyridyl)purin-6-amine] inhibits cytokine-induced expression of vascular endothelial growth factor-A, epiregulin, amphiregulin, and basic fibroblast growth factor mRNA in both RA-FLS and FLS. RA-FLS cell migration, along with cytokine-induced RA-FLS cell proliferation, and the RA-FLS invasive phenotype were significantly attenuated by GNF351 exposure. These findings indicate that inhibition of AHR activity may be a viable therapeutic target in amelioration of disease progression in RA.
See article at J Pharmacol Exp Ther 2014, 348:236–245.
- Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics