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 |
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頁(從 - 到) | 687-692 |
頁數 | 6 |
期刊 | Nature Medicine |
卷 | 7 |
發行號 | 6 |
DOIs | |
出版狀態 | 已發佈 - 2001 |
對外發佈 | 是 |
ASJC Scopus subject areas
- 生物化學、遺傳與分子生物學 (全部)
- 醫藥 (全部)