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dc.contributor.authorMarks, Ryanen
dc.date.accessioned2020-05-21T18:56:49Z
dc.date.available2020-05-21T18:56:49Z
dc.identifier.urihttp://hdl.handle.net/1974/27836
dc.description.abstractEndometriosis is an inflammatory gynaecological disease that affects 1 in 10 women globally. Characterized by the presence of endometrial-like tissues found proliferating outside the uterus, the disease is associated with chronic inflammation in the form of increased peritoneal cytokines and leukocyte populations, notably macrophages. Although several studies to date have highlighted the critical roles of macrophages in the progression of endometriosis and the promotion of peritoneal inflammation, the factors responsible for their recruitment and activation remained elusive. Through clinical observations, interleukin (IL)-33 was confirmed as to be a novel endometriosis-related damage-associated molecular pattern and herein we provided a characterization of its role in the regulation of macrophage activation and facilitation of lesion development in a mouse model of endometriosis. We provided evidence that IL-33, along with monocyte/macrophage-related chemotactic factor, monocyte chemoattractant protein-1 (MCP-1), were significantly increased within human endometriotic lesions compared to control endometrium. Evaluation of eutopic endometrium from women with endometriosis demonstrated macrophages were present in significantly greater abundance than control and may be central to promoting eutopic inflammation. Additionally, with emerging roles of the NLRP3 inflammasome in chronic inflammatory conditions, we sought to evaluate endometriosis patient peritoneal fluid and plasma by multiplex cytokine array and found aberrations in functional inflammasome products and regulators. Studies in our syngeneic, immunocompetent mouse model of endometriosis demonstrated that the administration of recombinant IL-33 induced significant lesion neovascularization and proliferation, as well as promoted robust peritoneal inflammation through the activation of macrophages. Furthermore, we found that inflammatory macrophage recruitment was regulated by the MCP-1/CCR2 signalling axis and was significantly attenuated by MCP-1 neutralization, which resulted in systemic and local perturbation in inflammation. These findings provided novel insights into the mechanisms regulating macrophage recruitment and activation which ultimately promoted endometriotic lesion development and inflammation in vivo.en
dc.language.isoengen
dc.relation.ispartofseriesCanadian thesesen
dc.rightsQueen's University's Thesis/Dissertation Non-Exclusive License for Deposit to QSpace and Library and Archives Canadaen
dc.rightsProQuest PhD and Master's Theses International Dissemination Agreementen
dc.rightsIntellectual Property Guidelines at Queen's Universityen
dc.rightsCopying and Preserving Your Thesisen
dc.rightsThis publication is made available by the authority of the copyright owner solely for the purpose of private study and research and may not be copied or reproduced except as permitted by the copyright laws without written authority from the copyright owner.en
dc.rightsAttribution-NonCommercial-NoDerivs 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/us/*
dc.subjectEndometriosisen
dc.subjectMacrophageen
dc.subjectIL-33en
dc.subjectMCP-1en
dc.titleImplications of macrophage recruitment and activation in the immunopathophysiology of endometriosisen
dc.typethesisen
dc.description.degreeM.Sc.en
dc.contributor.supervisorTayade, Chandrakant
dc.contributor.departmentBiomedical and Molecular Sciencesen
dc.embargo.termsThesis contains unpublished observations relevant to continuation of our research program.en
dc.embargo.liftdate2025-05-21T17:53:43Z
dc.degree.grantorQueen's University at Kingstonen


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Queen's University's Thesis/Dissertation Non-Exclusive License for Deposit to QSpace and Library and Archives Canada
Except where otherwise noted, this item's license is described as Queen's University's Thesis/Dissertation Non-Exclusive License for Deposit to QSpace and Library and Archives Canada