Dcr3 Expressed in Rheumatoid Synovial Fibroblasts Protects the Cells from Fas-induced Apoptosis

S. Hayashi., Y. Miura., T. Nishiyama., Y. Sakai., R. Kuroda., R. Saura., M. Kurosaka. Dept. of Orthopaedic Surgery, Kobe Univ. Graduate School of Med., Kobe, Japan [email protected] Introduction Decoy receptor 3 (DcR3)/TR6/M68 is a member of the tumor necrosis factor receptor (TNFR) superfamily. DcR3 lacks the transmembrane domain of conventional TNFRs to be a secreted protein. DcR3 is overexpressed in a variety of tumors, including lung and colon cancers, gliomas, gastrointestinal tract tumors, autoimmune tissues, and virus-associated leukemia. Over expression of DcR3 might benefit tumors by helping them avoid cytotoxic and regulatory effects of FasL, LIGHT, and TL1A. Meanwhile, rheumatoid arthritis (RA) is the inflammatory joint disease characterized by hyperplasia of synovial tissue and pannus formation growing invasively into the cartilage, followed by cartilage and bone destruction. Analyses of hyperplastic synovial tissues of patients with RA reveal features of transformed long-living cells such as somatic mutations, expression of oncogenes, and resistance to apoptosis. The resistance to apoptosis further contributes to synovial hyperplasia and is closely linked to the invasive phenotype of rheumatoid synovial fibroblasts (RA-SFs). We hypothesize that DcR3 may contribute to the pathogenesis of RA to be a noble therapeutic intervention for RA. In this study, we investigated DcR3 expression in RA-SFs and analyzed the function of DcR3 to cell apoptosis induced by Fas.