Statins selectively inhibit leukocyte function antigen-1 by binding to a novel regulatory integrin site

Gabriele Weitz-Schmidt, Karl Welzenbach, Volker Brinkmann, Tetsji Kamata, Joerg Kallen, Christian Bruns, Sylvain Cottens, Yoshikazu Takada, Ulrich Hommel

研究成果: 雜誌貢獻文章同行評審

926 引文 斯高帕斯(Scopus)

摘要

The β2 integrin leukocyte function antigen-1 (LFA-1) has an important role in the pathophysiology of inflammatory and autoimmune diseases. Here we report that statin compounds commonly used for the treatment of hypercholesterolemia selectively blocked LFA-1-mediated adhesion and costimulation of lymphocytes. This effect was unrelated to the statins' inhibition of 3-hydroxy-3-methylglutaryl coenzyme-A reductase; instead it occurred via binding to a novel allosteric site within LFA-1. Subsequent optimization of the statins for LFA-1 binding resulted in potent, selective and orally active LFA-1 inhibitors that suppress the inflammatory response in a murine model of peritonitis. Targeting of the statin-binding site of LFA-1 could be used to treat diseases such as psoriasis, rheumatoid arthritis, ischemia/reperfusion injury and transplant rejection.

原文英語
頁(從 - 到)687-692
頁數6
期刊Nature Medicine
7
發行號6
DOIs
出版狀態已發佈 - 2001
對外發佈Yes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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