Lay Summary

Proposal No. IBD-0176R
Principal Investigator:  Huabao Xiong, Ph.D.
Applicant Organization:  Mount Sinai School of Medicine (New York, New York, U.S.A.)
Project Title:   Blocking TLR signaling pathway by TLR peptides in the treatment of colitis
Period of Award:  March 15, 2006 – September 30, 2008

Immune cells responding to bacterial and viral pathogens express many proinflammatory molecules. Toll-like receptors (TLR) play a central role in recognition of these pathogens and hence control the degree of inflammation as well as the character of the inflammatory response. We have synthesized peptides that mimic a critical cytoplasmic part of the TLR. These peptides block TLR activation, cytokine production, and death from septic shock. To study the feasibility of using the peptides as a therapy for CD, we will test the ability of peptides to alter the course of colitis in the IL-10 knockout and trinitrobenzene sulfonic acid (TNBS)-induced murine models of Crohn’s disease. We will also study the effects of peptides on TLR interaction with other proteins important for signaling. In addition, we will test the effects of TLR peptides on maturation of dendritic cells, which are important to generate immune response. These experiments will validate the use of these novel peptide reagents to treat Crohn’s disease.