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A Newly Identified Immunosuppressive Protein In Rheumatoid Arthritis

Date:
March 28, 2007
Source:
John Wiley & Sons, Inc.
Summary:
The findings of a new study expose DcR3 as one of the factors culpable for RA's hallmark hyperplasia and its crippling consequences.
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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 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 were incubated with the proinflammatory TNFá prior to Fas-induced apoptosis, and apoptosis was measured.

DcR3 was expressed in both the RA and OA FLS, with no significant quantitative differences found between the samples. However, TNFá increased DcR3 expression in and inhibited Fas-induced apoptosis in RA FLS, but not in OA FLS.

This study affirms DcR3 as an immunosuppressive agent that actually protects destructive rheumatoid synovial cells against death. "We suggest that DcR3 expressed in RA FLS is increased by TNFá, making it one of the pathologic factors that induces hyperplasia of rheumatoid synovium," states researcher and author, Dr. Yasushi Miura. "Thus, strategies aimed at down-regulation of DcR3 in FLS warrant further investigation as a possible therapeutic approach in RA."

Even in this era of TNF-alpha inhibitors and other powerful drugs, there are constantly new aspects of biology being found that offer different forms of treatments for rheumatoid arthritis.

Article: "Decoy Receptor 3 Expressed in Rheumatic Synovial Fibroblasts Protects the Cells Against Fas-Induced Apoptosis," Shinya Hayashi, Yasushi Miura, Takayuki Nishiyama, Makoto Mitani, Koji Tateishi, Yoshitada Sakai, Akira Hashiramoto, Masahiro Kurosaka, Shunichi Shiozawa, and Minoru Doita, Arthritis & Rheumatism, April 2007; (DOI: 10.1002/art.22494).


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John Wiley & Sons, Inc.. "A Newly Identified Immunosuppressive Protein In Rheumatoid Arthritis." ScienceDaily. ScienceDaily, 28 March 2007. <www.sciencedaily.com/releases/2007/03/070328073217.htm>.
John Wiley & Sons, Inc.. (2007, March 28). A Newly Identified Immunosuppressive Protein In Rheumatoid Arthritis. ScienceDaily. Retrieved May 23, 2015 from www.sciencedaily.com/releases/2007/03/070328073217.htm
John Wiley & Sons, Inc.. "A Newly Identified Immunosuppressive Protein In Rheumatoid Arthritis." ScienceDaily. www.sciencedaily.com/releases/2007/03/070328073217.htm (accessed May 23, 2015).

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