Date on Master's Thesis/Doctoral Dissertation

5-2016

Document Type

Doctoral Dissertation

Degree Name

Ph. D.

Department

Microbiology and Immunology

Degree Program

Microbiology and Immunology, PhD

Committee Chair

Suttles, Jill

Committee Co-Chair (if applicable)

Egilmez, Nejat

Committee Member

Egilmez, Nejat

Committee Member

Mitchell, Thomas

Committee Member

Zhang, Huang Ge

Committee Member

McClain, Craig

Author's Keywords

Inflammatory bowel disease; Crohn's disease; ulcerative colitis; EGCG; green tea polyphenols

Abstract

This dissertation explores the role of epigallocatechin-3-gallate (EGCG), as a potential treatment for patients with inflammatory bowel disease (IBD). IBD is a common disorder that causes a great deal of suffering. Our understanding of the etiologies, pathogenic mechanisms, and treatment targets continues to evolve. Many new therapeutic targets are making their way through the pharmaceutical pipelines. However, not all patients benefit from these therapies. EGCG has long been studied as an anti-cancer agent. Most of our understanding of this compound comes from the oncologic literature. As the pathways of oncology and inflammation converge, new lessons can be taken from the cross discipline. EGCG’s effects on intracellular signaling bridges cancer to inflammation. Many of the same cytokines, chemokines, and molecular signals influencing cancer cells to grow also stimulate immune cells. Chapter 3 first explores the role of EGCG as both a preventative as well as a therapeutic agent and its effect on the dextran sulfate sodium (DSS) mouse model of colitis. The influence of EGCG on immune cell function is then explored in chapter 4. One novel approach in chapter 4 has to do with a focus on intestinal epithelial cells as agents of an immune response, and how EGCG impacts their function in that role. Chapter 5 explores the impact of EGCG on bolstering barrier function, as this is an important aspect of inflammatory bowel disease that is often neglected when considering new approaches to treating IBD. Finally, chapter 6 ends this dissertation with the first clinical trial in the world’s literature to evaluate EGCG as a therapeutic for IBD.

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