Lay Summary

Proposal No. IBD-0017
Principal Investigator:  Lawrence J. Saubermann, M.D.
Applicant Organization:  Boston Medical Center (Massachusetts, U.S.A.)
Project Title:  Immune modulation effects of PPARgamma in inflammatory bowel disease
Period of Award:  August 1, 2002 - July 31, 2004

Chronic human inflammatory bowel diseases (IBD), such as Crohn’s disease and ulcerative colitis, are associated with significant pain and suffering for millions of people.  These diseases are routinely identified through the use of clinical, radiologic, endoscopic, and tissue examinations.  One of the characteristic features of these disorders is the presence of particular forms of activated white blood cells, known as T cells, which move into the areas of inflammation.  These T cells can be further identified by specific surface markers and their use of receptors, which direct their movement and their response to substances released by inflamed intestines.  The generally held view of IBD is that the intestinal immune response to someone’s own bacteria is abnormal.  Based on this concept, therapies for IBD are being targeted at reducing the inflammatory substances and inhibiting the movement of T cells involved in the disease.  Essentially, therapy is being aimed at shifting the intestinal immune system back into a normal state of balance.

Recently, an important regulator of genes that are involved in inflammation, known as peroxisome-proliferator activated receptor-gamma (PPARγ), has been found to be increased in intestinal tissues.  Studies performed in mice have shown that when PPARγ is activated by specific medications normally used in the treatment of the adult form of diabetes, there is a decrease in intestinal inflammation.  Our preliminary studies have indicated that once PPARγ is stimulated, there is a significant reduction of the specific substances that cause T cells to move towards a site of inflammation.  There is also a decrease in the T cells’ surface receptor levels that allow them to respond to these inflammatory substances.  Therefore, we plan to investigate in greater detail the potential use of PPARγ activation to affect the movement of T cells and the substances that attract them.  By gaining insight into these effects, it may be possible to use these medications in IBD in order to prevent episodes of inflammation from occurring.