Date of Award
2026
Degree Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
Department
Molecular and Cellular Biochemistry Program
First Advisor
Mashkoor Choudhry
Abstract
Alcohol consumption has been found to worsen the pathology of colitis. The goal of this study was to investigate the mechanisms that underlie the exacerbation of colitis by ethanol. Using RNA sequencing, we identified increases in the reactive oxygen species (ROS) and reactive nitrogen species (RNS) proteins NOS2, CYBB, and NCF1 in the intestinal epithelial cells (IECs) in mice exposed to the colitis inducing agent dextran sulfate sodium (DSS) and followed by ethanol exposure. This is suggestive that ethanol may worsen the colitis pathology by increasing the oxidative stress. Using miRNA sequencing, we also identified differentially expressed miRNAs in the colonic IECs of mice exposed to both DSS and ethanol. Specifically, we focused on miR-410-3p as it was predicted to target NOS2. We therefore administered a miR-410-3p mimic to our mouse model and observed improvements in pathology, although the mechanism does not appear to be through NOS2 regulation. We previously found that IL-22 administration can reduce the pathology associated with ethanol exacerbated colitis. To elucidate the downstream effect of IL-22 treatment, we profiled NOS2, CYBB, and NCF1 expression and found that IL-22 reduces the expression of all three genes. IL-22 can signal through STAT3 activation, and we found that IL-22 administration in an IEC specific STAT3 -/- resulted in an improvement of most pathological measures. Next, studying IEC specific STAT3 -/- mice alone, we found improvement in all pathological scores and a reduction in inflammatory genes including our genes of interest NOS2, CYBB, and NCF1. While further investigation is necessary to understand the full mechanism, the results of this study further the understanding of how drinking alcohol can worsen colitis pathology.
Recommended Citation
Tschann, Madison, "Mechanisms of Ethanol Exacerbation of Colitis" (2026). Dissertations. 4320.
https://ecommons.luc.edu/luc_diss/4320
