Chromofungin ameliorates colitis and reduces endoplasmic reticulum stress and P53-apoptotic pathways

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dc.contributor.authorDiarra, Abdoulaye
dc.contributor.examiningcommitteeUzonna, Jude (Immunology) Mishra, Suresh (Physiology and Pathophysiology)en_US
dc.contributor.supervisorGhia, Jean-Eric (Immunology)en_US
dc.date.accessioned2020-09-08T15:13:31Z
dc.date.available2020-09-08T15:13:31Z
dc.date.copyright2020-09-07
dc.date.issued2020-08-26en_US
dc.date.submitted2020-08-27T20:08:37Zen_US
dc.date.submitted2020-09-08T03:50:00Zen_US
dc.degree.disciplineImmunologyen_US
dc.degree.levelMaster of Science (M.Sc.)en_US
dc.description.abstractCrohn’s disease (CD) and ulcerative colitis (UC) are chronic idiopathic inflammatory bowel diseases (IBD) with an estimated prevalence in Canada of around 15/100000 persons. Biological agents are expensive, require indefinite use to ensure a sustained response, and raise concerns about infections and other complications thus limiting enthusiasm for introducing them earlier in the treatment for IBD. The essential cells in the innate immune system that coordinates the inflammatory process are the macrophages (MØ), where MØs have been demonstrated to be increased in areas of inflammation in IBD. MØs are a heterogeneous population of two different phenotypes: group 1: “inflammatory, classically activated MØs: M1” and alternative activated MØs: M2. MØs polarization and plasticity depend on specific combinations of cytokines and peptides within the microenvironment. Mucosal changes in IBD are characterized by inflammation and are linked to hyperplasia in the chromogranin-A (CHGA)-producing enterochromaffin (EC) cells. CHGA cleavages generate several biologically active peptides, including chromofungin (CHGA47-66 [CFG]). Our lab demonstrated that CFG is an essential peptide in MØs regulation. Genome-wide associated studies in IBD have revealed that in IBD and within the epithelium, endoplasmic reticulum (ER) stress and intestinal epithelial apoptosis figure strikingly. A p53-apoptotic pathway mediates intestinal epithelial apoptosis through the activation of the p53-upregulated modulator of apoptosis (PUMA), Bcl-2 associated-X protein (BAX), Bcl-2 associated death promoter (BAD), Bcl-2 antagonist/killer-1 (BAK1), Caspase-3 and Caspase-8 proteins. Polymorphisms of X-box binding protein 1 (XBP1) gene, a main UPR signalling protein (GRP78), that develop enteritis and subsequent apoptotic cell death and is associated with an increased risk of IBD, The deletion of CHGA leads to an increase in GRP78 expression in diabetes. Currently, there is a gap of knowledge in understanding the influence of CHR on macrophages, ER stress, and apoptosis markers during the development of experimental colitis. Therefore, we hypothesize that Chromofungin plays a critical role in colonic inflammation via modulating ER stress and apoptotic pathways in macrophagesen_US
dc.description.noteOctober 2020en_US
dc.identifier.urihttp://hdl.handle.net/1993/34976
dc.language.isoengen_US
dc.rightsopen accessen_US
dc.subjectChromogranin-Aen_US
dc.subjectChromofunginen_US
dc.subjectGut hormonesen_US
dc.subjectColitisen_US
dc.subjectDendritic cellsen_US
dc.subjectCytokinesen_US
dc.subjectER stressen_US
dc.subjectApoptosisen_US
dc.titleChromofungin ameliorates colitis and reduces endoplasmic reticulum stress and P53-apoptotic pathwaysen_US
dc.typemaster thesisen_US
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