Seokchan Hong1, Eun-Jin Kim1, Eun-Ju Lee1, Bon San Koo1, Soo Min Ahn1, Seung-Hyeon Bae1, Doo-Ho Lim1, Yong-Gil Kim1, Bin Yoo1, Chang-Keun Lee2. 1. Division of Rheumatology, Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea. 2. Division of Rheumatology, Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea. Electronic address: cklee@amc.seoul.kr.
Abstract
AIMS: Rheumatoid arthritis (RA) is a chronic inflammatory arthritis that is characterized by hyperplastic synovial tissue containing activated synovial fibroblasts. Contradictory findings in the apoptosis of fibroblast-like synoviocytes (FLS) have been described elsewhere, showing that RA FLS have an enhanced susceptibility to Fas (also known as CD95)-mediated apoptosis in vitro in contrast to the observed lack of apoptosis in the RA synovium in vivo. However, the potential mechanisms responsible for this discrepancy remain under investigation. The soluble form of Fas (sFas) was found to inhibit Fas-induced apoptosis by binding to Fas ligand (FasL), thereby preventing the interaction between FasL and membrane-bound Fas. MAIN METHODS: We determined the levels of soluble FasL (sFasL) and sFas in patients with RA and the effects of proinflammatory mediators, including TNF-α, on the induction of apoptotic mediators in RA FLS. KEY FINDINGS: The levels of sFasL and sFas were significantly elevated in the synovial fluids of RA patients compared with control subjects. In addition, we found that the sFas is substantially induced in RA FLS by TNF-α, which were abundantly present in the synovial fluid of RA. SIGNIFICANCE: These findings suggest that TNF-α confers resistance to Fas-mediated apoptosis through sFas induction, which could explain the apparent resistance of RA synovial cells to apoptosis in vivo.
AIMS: Rheumatoid arthritis (RA) is a chronic inflammatory arthritis that is characterized by hyperplastic synovial tissue containing activated synovial fibroblasts. Contradictory findings in the apoptosis of fibroblast-like synoviocytes (FLS) have been described elsewhere, showing that RA FLS have an enhanced susceptibility to Fas (also known as CD95)-mediated apoptosis in vitro in contrast to the observed lack of apoptosis in the RA synovium in vivo. However, the potential mechanisms responsible for this discrepancy remain under investigation. The soluble form of Fas (sFas) was found to inhibit Fas-induced apoptosis by binding to Fas ligand (FasL), thereby preventing the interaction between FasL and membrane-bound Fas. MAIN METHODS: We determined the levels of soluble FasL (sFasL) and sFas in patients with RA and the effects of proinflammatory mediators, including TNF-α, on the induction of apoptotic mediators in RA FLS. KEY FINDINGS: The levels of sFasL and sFas were significantly elevated in the synovial fluids of RApatients compared with control subjects. In addition, we found that the sFas is substantially induced in RA FLS by TNF-α, which were abundantly present in the synovial fluid of RA. SIGNIFICANCE: These findings suggest that TNF-α confers resistance to Fas-mediated apoptosis through sFas induction, which could explain the apparent resistance of RA synovial cells to apoptosis in vivo.
Authors: Rita A Moura; Cláudia Quaresma; Ana R Vieira; Maria J Gonçalves; Joaquim Polido-Pereira; Vasco C Romão; Nádia Martins; Helena Canhão; João E Fonseca Journal: PLoS One Date: 2017-09-08 Impact factor: 3.240