Chapter 1 General Introduction
1.5 Aim of the study
Considering the importance of proper ER performance on the overall cellular fitness and function of the intestinal epithelium, it is crucial to understand the factors that trigger ER stress and the ensuing effects on the epithelial barrier. Furthermore, with the instances of IBD on the rise, it has become necessary to unravel the link between cytokine-induced inflammation, ER malfunction and intestinal disease. This study focuses on analyzing the effects of pro-inflammatory mediators on ER fitness and the subsequent influence of ER stress on intestinal epithelial cell polarity, protein folding and expression of intestinal proteins.
The purpose of this study is 1) to determine the ability of a cytokine cocktail made of TNF-α, IL-1, MCP-1 to induce ER stress 2) to investigate the effect of cytokine induced-ER stress on intestinal epithelial cell polarity, barrier integrity, protein folding and the expression of specific proteins from the apical membrane such as sucrase-isomaltase and ezrin, and from the basolateral membrane such as ZO-1, and Cx43 and 3) to explore the role of hypoxia-induced ER stress and its effect on barrier integrity.
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