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: Article査読

926 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)687-692
ページ数6
ジャーナルNature medicine
7
6
DOI
出版ステータスPublished - 2001
外部発表はい

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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