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

摘要: The beta2 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 treatment hypercholesterolemia selectively blocked LFA-1-mediated adhesion costimulation lymphocytes. This effect was unrelated to statins' inhibition 3-hydroxy-3-methylglutaryl coenzyme-A reductase; instead it occurred via binding a novel allosteric site within LFA-1. Subsequent optimization statins LFA-1 resulted potent, selective orally active inhibitors suppress response murine model peritonitis. Targeting statin-binding could be treat diseases such as psoriasis, rheumatoid arthritis, ischemia/reperfusion injury transplant rejection.