We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Statins selectively inhibit leukocyte function antigen-1 by binding to a novel regulatory integrin site.
- Authors
Weitz-Schmidt, G; Welzenbach, K; Brinkmann, V; Kamata, T; Kallen, J; Bruns, C; Cottens, S; Takada, Y; Hommel, U
- Abstract
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 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.
- Publication
Nature medicine, 2001, Vol 7, Issue 6, p687
- ISSN
1078-8956
- Publication type
Journal Article
- DOI
10.1038/89058