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: Masayasu Takahashi, Yasushi Miura, Shinya Hayashi, Koji Tateishi, Koji Fukuda, Masahiro Kurosaka
• Journal: International journal of molecular medicine (Int J Mol Med) Vol. 28 Issue 3 Pg. 423-7 (Sep 2011) ISSN: 1791-244X [Electronic] Greece
• PMID: 21537832 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Interleukin-1beta
• RNA, Messenger, Stored
• Receptors, Tumor Necrosis Factor, Member 6b
• TNFRSF6B protein, human
• TNFSF15 protein, human
• Tumor Necrosis Factor Ligand Superfamily Member 15
• Tumor Necrosis Factor-alpha

Topics

• Apoptosis
• Arthritis, Rheumatoid (pathology)
• Blotting, Western
• Cell Proliferation
• Fibroblasts (metabolism)
• Humans
• Interleukin-1beta (metabolism)
• RNA, Messenger, Stored
• Receptors, Tumor Necrosis Factor, Member 6b (genetics, metabolism)
• Signal Transduction
• Synovial Membrane (metabolism)
• Tumor Necrosis Factor Ligand Superfamily Member 15 (genetics, metabolism)
• Tumor Necrosis Factor-alpha (metabolism)