Lay Summary

Proposal No. IBD-0048
Principal Investigator:  Emiko Mizoguchi, M.D., Ph.D.
Applicant Organization:  Massachusetts General Hospital (Boston, U.S.A.)
Project Title:  Role of tumor necrosis factor receptors of colonic epithelial cells in inflammatory bowel disease
Period of Award:  March 1, 2003 - May 31, 2005

Experimental models of intestinal inflammation have helped us understand the pathogenesis of inflammatory bowel disease (IBD).  We will study animal models of colitis and surgical specimens obtained from IBD patients to test the hypothesis that the interactions between tumor necrosis factor (TNF) and TNF receptors (TNFRs) are important in the development of IBD.  Furthermore, we will examine whether these interactions play a different role in ulcerative colitis (UC) and Crohn’s disease (CD), and in different cell types (colonic epithelial cells versus immune cells) expressing TNF receptors.
 
Neutralization of TNF-alpha with anti-TNF-alpha antibody is effective in the therapy of CD, but not UC.  In addition, some CD patients show resistance to this therapy.  Therefore, the studies proposed in this application will help our understanding of therapies based on blocking TNF-alpha/ TNFRs interactions.  It should be useful to show the exact mechanism of TNFR mediated reactions, which will provide a rationale for developing new therapeutic approach based on the modification of TNF-alpha/TNFRs interactions in human IBD.