Histone deacetylases in RA: epigenetics and epiphenomena

Reduced synovial expression of histone deacetylases (HDACs) is proposed to contribute to pathology in rheumatoid arthritis (RA) by enhancing histone-dependent access of transcription factors to promoters of inflammatory genes. In the previous issue of Arthritis Research & Therapy, Kawabata and colleagues provided independent evidence that HDAC activity is increased in the synovium and fibroblast-like synoviocytes (FLSs) of patients with RA and is paralleled by increased HDAC1 expression and synovial tumor necrosis factor-alpha (TNF alpha) production. Remarkably, stimulation of RA FLSs with TNFa specifically increases HDAC activity and HDAC1 expression, suggesting that changes in synovial HDAC activity and expression may be secondary to local inflammatory status