Département de microbiologie-infectiologie et d'immunologie
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Focuss on the functions of extracellular nucleotides, exerted through the activation of P2 receptors, with an emphasis on the enzymes that regulate their concentrations at the cell surface. We have identified, cloned and characterized 6 new genes, including the 1st member of a new family encoding enzymes called NTPDases. We are interested in the regulation of inflammation in response to pathogenic determinants, the migration of immune cells, the functions of leukocytes, the contraction of smooth muscles, and in particular the regulation of inflammation of the intestine with an emphasis on epithelial cells and on a potential treatment for inflammatory bowel disease. We uses animal models with KO mice as well as methods of cell biology (murine and human primary cells), pharmacology, biochemistry and immunology.
Technical Skills: Enzymatic assays for ectonucleotidases; production of antibodies (polyclonal and monoclonal) using cDNA immunization which are excellent for antibodies to the native form of proteins; Cell culture of primary intestinal cells from mice and human colons; organ bath for contraction assays
Réferences:
Salem, M., J. Lecka, J. Pelletier, D.G. Marconato, A. Dumas, L. Vallières, G. Brochu, B. Robaye, C. Jobin & J. Sévigny. (2022) NTPDase8 protects mice from intestinal inflammation by limiting P2Y6 receptor activation: Identification of a new pathway of inflammation for the potential treatment of IBD. Gut. 71(1): 43–54.
Kauffenstein, G., J. Pelletier, E.G. Lavoie, F. Kukulski, M. Martín-Satué, S.S. Dufresne, J. Frenette, C. Ribas Fürstenau, M.J. Sereda, B. Toutain, D. Henrion, R. Sullivan, C. Vial & J. Sévigny. (2014) Nucleoside triphosphate diphosphohydrolase-1 ectonucleotidase is required for normal vas deferens contraction and male fertility through maintaining P2X1 receptor function. J. Biol. Chem. 289: 28629-39.
Babou Kammoe, R.B., G. Kauffenstein, J. Pelletier, B. Robaye & J. Sévigny. (2021) NTPDase1 modulates smooth muscle contraction in mice bladder by regulating nucleotide receptor activation distinctly in male and female. Biomolecules. 2021, 11(2): 147.
Kukulski, F., F. Bahrami, F. Ben Yebdri, J. Lecka, M. Martín-Satué, S.A. Lévesque & J. Sévigny. (2011) NTPDase1 controls IL-8 production by human neutrophils. J. Immunol. 187: 644-53.
Bigonnesse, F., S.A. Lévesque, F. Kukulski, J. Lecka, S.C. Robson, M.J.G. Fernandes & J. Sévigny. (2004) Cloning and characterization of mouse nucleoside triphosphate diphosphohydrolase-8. Biochemistry 43(18): 5511-5519.
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