title: Decoy receptor 3 expressed in rheumatoid synovial fibroblasts protects the cells against Fas-induced apoptosis.
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.
  
  
  CONCLUSIONS
  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.
authors: Division of Orthopedic Sciences, Faculty of Health Sciences, Kobe University School of Medicine, Kobe, Japan.
authors: Shinya
authors: S
authors: Hayashi
authors: Yasushi
authors: Y
authors: Miura
authors: Takayuki
authors: T
authors: Nishiyama
authors: Makoto
authors: M
authors: Mitani
authors: Koji
authors: K
authors: Tateishi
authors: Yoshitada
authors: Y
authors: Sakai
authors: Akira
authors: A
authors: Hashiramoto
authors: Masahiro
authors: M
authors: Kurosaka
authors: Shunichi
authors: S
authors: Shiozawa
authors: Minoru
authors: M
authors: Doita
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001172:Arthritis, Rheumatoid / Q000473:pathology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D015536:Down-Regulation; D053222:Fas Ligand Protein / Q000494:pharmacology*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015870:Gene Expression; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000235:genetics / Q000378:metabolism; D000922:Immunotoxins / Q000494:pharmacology; D020287:In Situ Nick-End Labeling; D020370:Osteoarthritis, Knee / Q000473:pathology; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D053323:Receptors, Tumor Necrosis Factor, Member 6b / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013583:Synovial Membrane / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D014162:Transfection
chemical_list: D053222:Fas Ligand Protein; D007141:Immunoglobulin Fc Fragments; D000922:Immunotoxins; D034741:RNA, Small Interfering; D053323:Receptors, Tumor Necrosis Factor, Member 6b; D011993:Recombinant Fusion Proteins