THE ROLE OF ELASTASE/ELASTASE INHIBITOR IN DIALOG .. (EPIMACase)
THE ROLE OF ELASTASE/ELASTASE INHIBITOR IN DIALOG BETWEEN INTESTINAL EPITHELIAL CELLS AND MACROPHAGES IN INFLAMMATORY BOWEL DISEASES CONTEXT
Date du début: 6 août 2014,
Date de fin: 5 août 2016
Inflammatory Bowel Diseases (IBD) are chronic disorders for which aetiology is unknown and only palliative care is available for patients. In Europe, 2.2 million people suffered of ulcerative colitis or Crohn's disease in Europe, the socio-economic impact of IBD is very heavy. Thus, the development of new and more effective treatments for IBD depends upon a better understanding of the regulation of inflammatory response.The aims of this project are both: firstly, provide evidence of contribution of secreted elastase from intestinal epithelial cells (IEC) to over activation of macrophages in IBD and establish molecular actors of this crosstalk; secondly decipher the protective properties against colitis of ELAFIN, an elastase inhibitor, through modulation of macrophage activities. The fellow will develop in vitro and in vivo experiments to establish the role of elastolytic balance in the dialog between IEC and macrophages in relation to IBD.Our data raise the possibility that intestinal IEC are major regulators of proteolytic homeostasis by secreting proteases and protease inhibitors, which then can interfere with all biological functions of the gut, including immune functions. In IBD, secreted hyperactive elastase could participate to the dialogue between epithelium and other mucosal cells such as macrophages. Our analysis of elastase homeostasis aims to identify control points in the mechanisms of disease that could be addressed by development of a novel therapeutic approach for IBD.The fellow holds a junior investigator position at a French Institution. This program will allow her to develop complementary and transferable skills and to successfully build-up and conduct a ground-breaking research project in the field of human digestive health. This foreign experience is a necessary step on the road to complete independence for her. Thanks to this program, she would be in an optimal position to create an independent research group upon her return to Europe.
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