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EQUIPE 1 : PATHOPHYSIOLOGIE DE L’EPITHELIUM INTESTINAL
TEAM 1 : PATHOPHYSIOLOGY OF THE INTESTINAL EPITHELIUM |
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Recherche/projet research/project
Proteases from epithelial cells, mediators of inflammation in IBD
Tissue homeostasis is disrupted in a number of chronic diseases. In particular, proteolytic homeostasis which plays major roles in tissue remodelling and in digestive organ functions, is disrupted in inflammatory bowel disease (IBD). Therefore, a better knowledge of the actors involved in proteolytic homeostasis is a major step towards disease comprehension and diagnostic. Two types of molecules regulate proteolytic homeostasis: proteases and protease inhibitors, defining the proteolytic status of the tissues. The characterization of the proteases hyperactive in the inflamed gut, their substrates, and the consequences of their increased activity will advance our knowledge of the biological cascades initiated by protease dysregulation in IBD. We expect of our analysis of protease hyperactivity to identify control points in the mechanisms of disease that could be addressed by the development of specific inhibitors, as the basis of novel therapeutic approaches for IBD.
Tissue homeostasis is disrupted in a number of chronic diseases. In particular, proteolytic homeostasis which plays major roles in tissue remodelling and in digestive organ functions, is disrupted in inflammatory bowel disease (IBD). Therefore, a better knowledge of the actors involved in proteolytic homeostasis is a major step towards disease comprehension and diagnostic. Two types of molecules regulate proteolytic homeostasis: proteases and protease inhibitors, defining the proteolytic status of the tissues. The characterization of the proteases hyperactive in the inflamed gut, their substrates, and the consequences of their increased activity will advance our knowledge of the biological cascades initiated by protease dysregulation in IBD. We expect of our analysis of protease hyperactivity to identify control points in the mechanisms of disease that could be addressed by the development of specific inhibitors, as the basis of novel therapeutic approaches for IBD.
Production scientifique scientific production
- Basso L, Boué J, Mahiddine K, Blanpied C, Robiou-du-Pont S, Vergnolle N, Deraison C, Dietrich G. Endogenous analgesia mediated by CD4(+) T lymphocytes is dependent on enkephalins in mice. J Neuroinflammation. 2016 Jun 1;13(1):132
- Bermudez-Humaran, L & Motta, JP, Aubry C, Kharrat P. Rous-Martin L, Sallenave JM, Deraison C, Vergnolle N, Langella P. Serine protease inhibitors protect better than IL-10 and TGF-beta anti-inflammatory cytokines against mouse colitis when delivered by recombinant lactococci, Microbial Cell Factories, 2015 Dec;14(1):198.
- Bermúdez-Humarán LG, Aubry C, Motta JP, Deraison C, Steidler L, Vergnolle N, Chatel JM, Langella P. Engineering lactococci and lactobacilli for human health. Curr Opin Microbiol. 2013 Jul 11. S1369-5274(13)00076-3
- Motta JP & Bermúdez-Humarán LG, Deraison C, Martin L, Rolland C, Rousset P, Boue J, Dietrich G, Chapman K, Kharrat P, Vinel JP, Alric L, Mas E, Sallenave JM, Langella P, Vergnolle N. Food-grade bacteria expressing elafin protect against inflammation and restore colon homeostasis. Sci Transl Med. 2012 31;4(158) *Joint First Authors
