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You searched for +publisher:"University of North Carolina" +contributor:("Sheikh, Shehzad Zafar"). One record found.

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University of North Carolina

1. Sheikh, Shehzad Zafar. Defects in Macrophage Specific Homeostatic Pathways in the Inflammatory Bowel Diseases.

Degree: Microbiology and Immunology, 2010, University of North Carolina

Intestinal macrophages are specialized to carry out their functions in the local antigen- and microbiota-rich environment. They are refractory to the induction of proinflammatory cytokines, yet still display potent phagocytic and bactericidal activity. These adaptations allow the intestinal macrophage to eradicate microbes that breach the intestinal epithelial barrier while maintaining local tissue homeostasis. The inflammatory bowel diseases, Crohn’s disease and ulcerative colitis, results from an inappropriately directed inflammatory response to the enteric microbiota in a genetically susceptible host. In contrast to the characteristic anti-inflammatory phenotypic and functional profile of normal intestinal macrophages, these macrophages react to luminal microbes and become potent producers of proinflammatory cytokines such as IL-12 family members. IL-12 and 23 are heterodimeric cytokines produced by macrophages and dendritic cells that are important bridges between innate and adaptive immunity. Although the molecular events that lead to the expression of IL-12 and Il-23 in macrophages through TLR signaling have been well defined, anti-inflammatory pathways that lead to inhibition of these cytokines in macrophages have not been fully elucidated. We identify two important homeostatic pathways; IFN-γ and HO-1 that regulate enteric microbiota-induced production of IL-12 and 23 by macrophages. IFN-γ inhibits TLR induced IL-23 expression in macrophages, and these events prevent the initiation and progression of spontaneous IL-23-driven experimental colitis in IL-10 deficient (IL-10-/-) mice. Moreover, we demonstrate that enteric microbiota-induced heme-oxygenase 1 (HO- 1) is critical in the prevention of experimental colitis, through inhibition of IL-12 family members and augmentation of macrophage microbicidal pathways. In our first study we demonstrate that IFN-γ has anti-inflammatory properties in murine models of Th1/Th17 mediated experimental colitis through attenuation of TLRmediated IL-23 expression in macrophages. In the second series of experiments, using germ-free WT and colitis-prone IL-10-/- mice we show that intestinal HO-1 expression induced by the enteric microbiota is an important homeostatic pathway. We also identify signaling pathways (MyDD88, MAPK and Pi3K) essential for HO-1 induction in macrophages. Finally, in our third study, protective effects of the HO-1 pathway were determined in Th2-mediated chronic colonic inflammation in T cell receptor- alpha (TCRα) deficient (-/-) mice. TCRα-/- mice exposed to carbon monoxide (CO) or treated with a pharmacologic HO-1 inducer demonstrated significant amelioration of active colitis. We demonstrate that HO-1 regulates mucosal innate immune responses in the TCRα-/- mouse through IL-10 induction in colonic macrophages. Advisors/Committee Members: Sheikh, Shehzad Zafar, Plevy, Scott E., University of North Carolina at Chapel Hill.

Subjects/Keywords: School of Medicine; Department of Microbiology and Immunology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Sheikh, S. Z. (2010). Defects in Macrophage Specific Homeostatic Pathways in the Inflammatory Bowel Diseases. (Thesis). University of North Carolina. Retrieved from https://cdr.lib.unc.edu/record/uuid:e9f3f872-ae20-4d52-b298-16b98164daa8

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

Sheikh, Shehzad Zafar. “Defects in Macrophage Specific Homeostatic Pathways in the Inflammatory Bowel Diseases.” 2010. Thesis, University of North Carolina. Accessed October 31, 2020. https://cdr.lib.unc.edu/record/uuid:e9f3f872-ae20-4d52-b298-16b98164daa8.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Sheikh, Shehzad Zafar. “Defects in Macrophage Specific Homeostatic Pathways in the Inflammatory Bowel Diseases.” 2010. Web. 31 Oct 2020.

Vancouver:

Sheikh SZ. Defects in Macrophage Specific Homeostatic Pathways in the Inflammatory Bowel Diseases. [Internet] [Thesis]. University of North Carolina; 2010. [cited 2020 Oct 31]. Available from: https://cdr.lib.unc.edu/record/uuid:e9f3f872-ae20-4d52-b298-16b98164daa8.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Sheikh SZ. Defects in Macrophage Specific Homeostatic Pathways in the Inflammatory Bowel Diseases. [Thesis]. University of North Carolina; 2010. Available from: https://cdr.lib.unc.edu/record/uuid:e9f3f872-ae20-4d52-b298-16b98164daa8

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

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