title: DcR3-TL1A signalling inhibits cytokine-induced proliferation of rheumatoid synovial fibroblasts.
abstract: Decoy receptor 3 (DcR3), a member of the tumour necrosis factor receptor (TNFR) superfamily, lacks the transmembrane domain of conventional TNFRs in order to be a secreted protein. DcR3 competitively binds and inhibits members of the TNF family, including Fas ligand (FasL), LIGHT and TL1A. We previously reported that TNFα-induced DcR3 overexpression in rheumatoid synovial fibroblasts (RA-FLS) protects the cells from Fas-induced apoptosis and that DcR3 induces VLA-4 expression in THP-1 macrophages to inhibit cycloheximide-induced apoptosis. Meanwhile, recent studies have suggested that DcR3 acting as a ligand directly induces the differentiation of macrophages to osteoclasts. Therefore, in the present study, we analyzed the direct effects of DcR3 as a ligand in RA-FLS. The experiments showed that DcR3 binds to TL1A expressed in RA-FLS resulting in the negative regulation of cell proliferation induced by inflammatory cytokines. DcR3-TL1A signalling may be involved in the pathogenesis of rheumatoid arthritis (RA).
authors.affiliation: Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Chuo-ku, Kobe 650-0017, Japan.
authors.forename: Masayasu
authors.initials: M
authors.lastname: Takahashi
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Miura
authors.forename: Shinya
authors.initials: S
authors.lastname: Hayashi
authors.forename: Koji
authors.initials: K
authors.lastname: Tateishi
authors.forename: Koji
authors.initials: K
authors.lastname: Fukuda
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kurosaka
mesh_terms: D017209:Apoptosis; D001172:Arthritis, Rheumatoid / Q000473:pathology*; D015153:Blotting, Western; D049109:Cell Proliferation; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism; D023121:RNA, Messenger, Stored; D053323:Receptors, Tumor Necrosis Factor, Member 6b / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013583:Synovial Membrane / Q000378:metabolism*; D053380:Tumor Necrosis Factor Ligand Superfamily Member 15 / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D053583:Interleukin-1beta; D023121:RNA, Messenger, Stored; D053323:Receptors, Tumor Necrosis Factor, Member 6b; C505911:TNFRSF6B protein, human; C117026:TNFSF15 protein, human; D053380:Tumor Necrosis Factor Ligand Superfamily Member 15; D014409:Tumor Necrosis Factor-alpha