Title

Effect of Nicotine on IL-1 Induced MMP-3 Expression: Role of a Polymorphic Promoter Element

Date of Award

2013

Degree Type

Thesis

Degree Name

Master of Science in Biomedical Sciences

First Advisor

Ruth Borghaei, PhD

Second Advisor

Farzaneh Daghigh, PhD

Third Advisor

Michael McGuinness, PhD

Fourth Advisor

Marcus Bell, PhD

Abstract

MMP-3 is an extracellular matrix remodeling protease. It is involved in normal tissue remodeling associated with physiological processes such as development and wound healing, however its production can become dysregulated in several pathological conditions, resulting in tissue degradation (excess production) or fibrosis (decreased production). Both homozygous forms of the 5T/6T polymorphic promoter element found on the MMP-3 gene have been linked to increased risk or progression of various pathogenic diseases. Smokers canying the 5T allele have been shown to exhibit increased progression to cardiac diseases and risk of oral cancer relative to smokers homozygous for the 6T form. The experiments described here were designed to determine the effects of nicotine on IL-l induced production of MMP-3, and whether the polymorphic promoter region is involved. Experiments were designed which determined the protein and mRNA levels of iL-1 and/or nicotine induced MMP-3 production. The role of the nicotine and the polymorphic promoter element was examined through transient transfection experiments in which a luciferase reporter assay was used to measure the levels of transcription from the MMP-3 promoter. There appeared to be a significant IL-l induction ofMMP-3 production in the protein, mRNA, and transfection results. However, there did not seem to be a significantly large synergistic increase with nicotine and IL-l on MMP-3 production.

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