Drug Design for Treatment of Inflammatory Bowel Disease

Excessive infiltration of lymphocytes has been implication in the pathogenesis of several inflammatincluding inflammatory bowel disease (IBD). The mucosal vascular addressing, MAdCAM-1 is a tissue spreceptor selectively expressed in high endothelial venules (HEVs) in mucosal lymphoid tissues includand, to a lesser extent, small venules in the lamina propria. Cell adhesion assays and in vitro homishown that the alpha4beta7 integrin, expressed on both B and T cell subsets, defines a mucosal hominpreferentially interacts with MAdCAM-1. Preliminary immunocytochemistry has shown lymphocytic infiltalpha4beta7 and increased expression of MAdCAM-1 in intestinal tissues of murine models of IBD and sinfiltrates in human tissue as well. Recently developed murine models of IBD will provide a key steptherapeutic strategies to inhibit these receptor-counter receptor interactions which have been impliIBD. Furthermore, a high throughput drug screen will be set up to identify and develop small moleculreceptors. This proposal will therefore lay the foundation for a new class of anti inflammatory drug