Tumor necrosis factor-alpha (TNF-alpha) converting enzyme contributes to production of TNF-alpha in synovial tissues from patients with rheumatoid arthritis.

Abstract

Expression and function of tumor necrosis factor-alpha (TNF-alpha) converting enzyme (TACE) in synovia of patients with rheumatoid arthritis (RA) were examined to investigate posttranslational regulation of TNF-alpha production by TACE in RA. Expression of TACE protein was evaluated by immunohistochemistry. Cytokines and soluble cytokine receptors were measured by ELISA. TACE mRNA was detected by RT-PCR. The enzymatic activity of TACE was measured using TACE-specific fluorogenic substrate. Expression of TACE at protein level in synovial tissue (ST) of patients with RA was significantly stronger than that of patients with osteoarthritis (OA). In RA, TACE was mainly expressed in CD68+ macrophage-like synovial cells. ST from 9 of 9 RA and 3 of 8 OA patients expressed TACE mRNA. RA ST cells possessed significantly higher TACE-like enzymatic activity than OA ST. A synthetic TACE inhibitor significantly reduced the release of TNF-alpha and p75 TNF receptor from RA ST cells. TACE is an important regulator of the secretion of TNF-alpha from synovia of patients with RA.