Regulation of Interleukin-1 -Induced Interleukin-6 Gene Expression in Human Fibroblast-Like Synoviocytes by Glucocorticoids

Abstract

Involvement of interleukin-6 (IL-6) in the pathogenesis of rheumatoid arthritis (RA) has recently been demonstrated. In the present study, the regulation of IL-6 gene expression by glucocorticoids and IL-1β in fibroblast-like synoviocytes (FLSs) was investigated. Both synthetic and natural glucocorticoids, i.e., dexamethasone (DEX) and hydrocortisone (HC), respectively, concentration-dependently inhibited protein production and gene expression of IL-6 by human FLSs. The effect of DEX was dependent on de novo protein synthesis. DEX significantly reduced the rate of IL-6 gene transcription without affecting the stability of IL-6 mRNA. The IxBα pathway seemed not to be involved in DEX-mediated inhibition of IL-6 gene expression in IL-1β-stimulated human FLSs. These findings suggest that glucocorticoids suppress IL-6 gene transcription by an as yet undefined mechanism.