( A complex autoimmune disease rheumatoi...)A Newly Identified Immunosuppressive Protein in Rheumatoid Arthritis,Health

A complex autoimmune disease, rheumatoid arthritis (RA) is characterized by chronic inflammation and progressive joint damage. This process begins with hyperplasia//, or excessive increase in size and thickness, of synovial tissue. Along with provoking cartilage and bone destruction, this abnormal tissue growth is resistant to apoptosis, the natural cell death vital to the generation of healthy new cells.

Decoy receptor 3 (DcR3) is a newly identified member of the tumor necrosis factor receptor (TNFR) superfamily. A soluble protein, it is overexpressed in tumor cells, including lung and colon cancers, gastrointestinal tract tumors, and leukemia. It is also expressed in a variety of normal tissue—the colon, lung, stomach, spleen, lymph node, pancreas, and spinal cord. Because rheumatoid synovial cells share traits with tumor cells—both are resistant to apoptosis, both proliferate aggressively— DcR3 might play a role in the destructive course of RA. To investigate this possibility, researchers at Kobe University School of Medicine in Japan conducted the first study of DcR3 expression in RA fibroblast-like synoviocytes (FSL)—cells in the synovial membrane instrumental to the production of cartilage as well as synovial fluid. Featured in the April 2007 issue of Arthritis & Rheumatism (http://www.interscience.wiley.com/journal/arthritis), their findings expose DcR3 as one of the factors culpable for RA's hallmark hyperplasia and its crippling consequences.

For their novel study of DcR3, the researchers isolated and cultured FLS from 19 patients with RA, obtained during total knee replacement surgery. For comparison, FLS was also extracted in a similar manner from 14 patients with osteoarthritis (OA). For all samples, expression of DcR3 in FLS was measured by reverse-transcriptase-polymerase chain reaction and Western blotting. Then, apoptosis was induced by Fas, a protein ligand and member of the tumor necrosis factor (TNF) family. Finally, FLS we
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