ROLE OF CHEMOKINES IN INFLAMMATORY BOWEL DISEASE
Icahn School Of Medicine At Mount Sinai, New York NY
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Abstract
The increased infiltration of inflammatory cells (neutrophils, lymphocytes, macrophages and[unreadable] dendritic cells) into the gastrointestinal tract is a hallmark of both ulcerative colitis and[unreadable] Crohn's disease. The recruitment of these leukocytes may be controlled in part by a family[unreadable] of chemotactic cytokines, known as chemokines. We propose to investigate the functional[unreadable] role of chemokines in inflammatdry bowel disease and to examine if chemokine antagonism[unreadable] will alleviate or block inflammatory bowel disease.[unreadable] Specifically we will:[unreadable] 1) Define the functional contribution of chemokine receptors to IBD. We will define[unreadable] the functional relevance of individual chemokine receptors to inflammatory bowel disease[unreadable] using chemokine receptor knockout mice. Prioritization of target genes will be done on the[unreadable] basis of documented expression of these receptors in human IBD samples and in[unreadable] experimental models of IBD.[unreadable] 2) Define the functional contribution of chemokine ligands to IBD. We will define the[unreadable] functional relevance of chemokine ligands to inflammatory bowel disease using chemokine[unreadable] ligand knock-out mice. In addition, we will attempt to interfere with several chemokine[unreadable] networks at once. To this end we will use transgenic mice expressing the chemokine binding[unreadable] protein, M3.[unreadable] This work will provide insights on the role of chemokines in inflammatory bowel disease and[unreadable] will examine the therapeutic potential of the chemokine blockade to IBD.
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