Dihydrotestosterone Inhibits Tumor Necrosis Factor α Induced Interleukin-1α mRNA Expression in Rheumatoid Fibroblast-Like Synovial Cells

Abstract

Rheumatoid arthritis (RA) is a chronic inflammatory disease that affects multiple synovial joints. Proinflammatory cytokines, such as interleukin-1 (IL-1) and tumor necrosis factor (TNF)α play important roles as principle inflammatory and destructive components of the disease. RA is known to be associated with significant gender differences in its prevalence and clinical features. We found that a potent androgen, 5α-dihydrotestosterone (DHT) inhibits IL-1α mRNA expression induced by TNFα and the DHT effect was inhibited by an androgen receptor antagonist, hydroxyflutamide (OHF). DHT inhibited the NF-κB activation induced by TNFα in a manner dependent on the androgen receptor (AR). These results suggest that DHT inhibits the TNFα-induced IL-1α mRNA expression by inhibiting NF-κB activation, and contributes to the gender differences of the disease.