Catestatin (CTS) decreases intestinal inflammation in both acute and chronic models of murine colitis through the regulation of macrophages and/or gut microbiota

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dc.contributor.authorRabbi, Mohammad
dc.contributor.examiningcommitteeSoussi Gounni, Abdel (Immunology) Mishra, Suresh (Physiology and Pathophysiology) Khafipour, Ehsan (Animal Science) Asselin, Claude (Université de Sherbrooke)en_US
dc.contributor.supervisorGhia, Jean-Eric (Immunology)en_US
dc.date.accessioned2018-04-12T13:53:27Z
dc.date.available2018-04-12T13:53:27Z
dc.date.issued2014-06en_US
dc.date.issued2017-01en_US
dc.date.issued2016-09en_US
dc.date.issued2017-08en_US
dc.date.submitted2018-04-01T02:55:06Zen
dc.date.submitted2018-04-11T22:50:15Zen
dc.degree.disciplineImmunologyen_US
dc.degree.levelDoctor of Philosophy (Ph.D.)en_US
dc.description.abstractInflammatory bowel disease (IBD) is a chronic relapsing inflammatory disease of the gastrointestinal tract with unknown etiology. Although the incidence of IBD is increasing globally, there is no curative treatment for this complex disease. Therefore, revealing the etiology of IBD and identifying an optimal treatment is a major challenge. Mucosal changes in IBD are characterized by transmural inflammation and associated with an alteration in the prohormone chromogranin-A (CHGA) producing enterochromaffin (EC) cells. However, it is not clear whether the change plays any role in immune activation and in regulation of gut inflammation. The aim of this thesis was to identify the impact of catestatin (CTS), a bioactive peptide derived from the conserved C-terminal portion of CHGA on gut inflammation. In our first study, using an acute model of murine colitis and biopsy samples from ulcerative colitis (UC) patients, we demonstrated that CHGA and CTS were increased during inflammation. Moreover, we identified that administration of human (h) CTS significantly down- regulated gut inflammation. This down-regulation occurred via the modulation of pro-inflammatory cytokine secretion from the macrophage population. Although CTS is known as an antimicrobial peptide, there was no reported in vivo study demonstrating its antimicrobial impact in the gut. In our second study, we depicted that hCTS administration altered the gut microbiota composition, associated with a more prominent effect on the fecal microbiota than the mucosa-associated microbiota (MAM). In a separate study, we showed that the chemical agent (dextran sulfate sodium [DSS]), used in our colitis model, was also able to induce a microbial dysbiosis both in fecal and MAM samples. Finally, considering IBD as a relapsing disease of intestinal inflammation, we investigated the effect of hCTS in the context of intestinal inflammation reactivation using a chronic model of colitis mimicking the natural history of IBD. We observed that hCTS administration could down-regulate the reactivation of colitis through a down-regulation of the M1 but not the M2 macrophages and the gut microbiota. In conclusion, this Ph.D. thesis work revealed a novel anti-inflammatory effect of hCTS in gut inflammation which in the future might open novel therapeutic avenues for IBD.en_US
dc.description.noteMay 2018en_US
dc.identifier.citationRabbi MF, Eissa N, Munyaka PM, et al. Reactivation of Intestinal Inflammation Is Suppressed by Catestatin in a Murine Model of Colitis via M1 Macrophages and Not the Gut Microbiota. Frontiers in Immunology. 2017;8:985. doi:10.3389/fimmu.2017.00985.en_US
dc.identifier.citationRabbi MF, Munyaka PM, Eissa N, Metz-Boutigue M-H, Khafipour E, Ghia JE. Human Catestatin Alters Gut Microbiota Composition in Mice. Frontiers in Microbiology. 2016;7:2151. doi:10.3389/fmicb.2016.02151.en_US
dc.identifier.citationRabbi MF, Labis B, Metz-Boutigue M-H, Bernstein CN, Ghia JE Catestatin Decreases Macrophage Function in Two Mouse Models of Experimental Colitis. Biochemical Pharmacology. 2014;89(3):386. doi: 10.1016/j.bcp.2014.03.003en_US
dc.identifier.citationMunyaka PM, Rabbi MF, Khafipour E, Ghia JE. Acute Dextran Sulfate Sodium (DSS)-induced Colitis Promotes Gut Microbial Dysbiosis in Mice. Journal of Basic Microbiology. 2016;56(9):986. doi: 10.1002/jobm.201500726.en_US
dc.identifier.urihttp://hdl.handle.net/1993/32959
dc.language.isoengen_US
dc.publisherBiochemical pharmacologyen_US
dc.publisherFrontiers in microbiologyen_US
dc.publisherJournal of basic microbiologyen_US
dc.publisherFrontiers in immunologyen_US
dc.rightsopen accessen_US
dc.subjectCatestatinen_US
dc.subjectInflammatory bowel diseaseen_US
dc.subjectColitisen_US
dc.subjectMacrophagesen_US
dc.titleCatestatin (CTS) decreases intestinal inflammation in both acute and chronic models of murine colitis through the regulation of macrophages and/or gut microbiotaen_US
dc.typedoctoral thesisen_US
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