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

Objective. Expression and function of tumor necrosis factor-alpha (TNF-alph a) converting enzyme (TACE) in synovia of patients with rheumatoid arthriti s (RA) were examined to investigate posttranslational regulation of TNF-alp ha production by TACE in RA. Methods. 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. Results. Expression of TACE at protein level in synovial tissue (ST) of pat ients with RA was significantly stronger than that of patients with osteoar thritis (OA). In RA, TACE was mainly expressed in CD68+ macrophage-like. sy novial 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 th an OA ST. A synthetic TACE inhibitor significantly reduced the release of T NF-alpha and p75 TNF receptor from RA ST cells. Conclusion. TACE is an important regulator of the secretion of TNF-alpha fr om synovia of patients with RA.