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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Deng, G-M; Zheng, L; Chan, FK-M; Lenardo, M

Published Date

  • October 2005

Published In

Volume / Issue

  • 11 / 10

Start / End Page

  • 1066 - 1072

PubMed ID

  • 16170321

Pubmed Central ID

  • 16170321

Electronic International Standard Serial Number (EISSN)

  • 1546-170X

International Standard Serial Number (ISSN)

  • 1078-8956

Digital Object Identifier (DOI)

  • 10.1038/nm1304

Language

  • eng