Amelioration of inflammatory arthritis by targeting the pre-ligand assembly domain of tumor necrosis factor receptors.

Laboratory of Immunology, Building 10, Room 11N311, 10 Center Drive, MSC 1892, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, Maryland 20892, USA.
Nature Medicine (Impact Factor: 28.05). 11/2005; 11(10):1066-72. DOI: 10.1038/nm1304
Source: PubMed

ABSTRACT Tumor necrosis factor (TNF)-alpha has an important role in the pathogenesis of autoimmune and inflammatory diseases such as rheumatoid and septic arthritis. The biological effects of TNF-alpha are mediated by binding to TNF receptors TNFR1 (also known as P60) or TNFR2 (also known as P80). The pre-ligand assembly domain (PLAD) is a portion of the extracellular region of TNFRs that mediates receptor-chain association essential for signaling. We found that soluble versions of PLAD, especially those derived from P60, block the biochemical effects of TNF-alpha in vitro and potently inhibit arthritis in animal models. Thus, targeting the PLAD may have clinical value in the treatment of human arthritis and other disorders involving receptors of the TNFR superfamily.

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