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Decoy Receptor 3 Expressed in Rheumatoid Synovial Fibroblasts Protects the Cells Against Fas-induced Apoptosis

Decoy Receptor 3 Expressed in Rheumatoid Synovial Fibroblasts Protects the Cells Against Fas-induced Apoptosis

Shinya Hayashi, Yasushi Miura, Takayuki Nishiyama, Makoto Mitani, Koji Tateishi, Yoshitada Sakai, Akira Hashiramoto, Masahiro Kurosaka, Shunichi Shiozawa, Minoru Doita

Arthritis Rheum. 2007 Apr;56(4):1067-75.

PMID: 17393415

Abstract:

Objective:
Decoy receptor 3 (DcR3), a newly identified member of the tumor necrosis factor receptor (TNFR) superfamily, is a soluble receptor that binds to members of the TNF family, including FasL, LIGHT, and TNF-like molecule 1A. DcR3 is mostly expressed in tumor cells, and it competitively inhibits binding of TNF to TNFRs. The present study was undertaken to investigate DcR3 expression in fibroblast-like synoviocytes (FLS) from patients with rheumatoid arthritis (RA) and osteoarthritis (OA), and to analyze the effects of DcR3 on Fas-induced apoptosis in RA FLS.
Methods:
Expression of DcR3 in FLS was measured by reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blotting. FLS were incubated with DcR3-Fc chimera protein or transfected with DcR3 small interfering RNA (siRNA) using the lipofection method, before induction of apoptosis. Apoptosis induced by Fas in FLS was detected with TUNEL staining and Western blotting of caspase 8 and poly(ADP-ribose) polymerase. Finally, FLS were incubated with TNFalpha prior to Fas-induced apoptosis, expression of DcR3 was analyzed by quantitative RT-PCR, and apoptosis was measured.
Results:
DcR3 was expressed in both RA FLS and OA FLS. DcR3-Fc protein inhibited Fas-induced apoptosis in FLS. Down-regulation of DcR3 in FLS by siRNA increased Fas-induced apoptosis. TNFalpha increased DcR3 expression and inhibited Fas-induced apoptosis in RA FLS, but not in OA FLS.
Conclusion:
DcR3 expressed in RA FLS is increased by TNFalpha and protects the cells against Fas-induced apoptosis. These findings indicate that DcR3 may be a possible therapeutic target in RA.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR42412937	DcR3/Fc Chimera human			Price

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