Author

Brian Maddox

Date of Graduation

Summer 2015

Degree

Master of Science in Cell and Molecular Biology

Department

Biomedical Sciences

Committee Chair

Tyler Morris

Keywords

TNFa, converting enzyme, colitis, inflammation

Subject Categories

Medical Molecular Biology

Abstract

Tumor Necrosis Factor-a Converting Enzyme (TACE) induces active TNFa and may contribute to the development of colitis in humans. I hypothesized that pharmacological blockade of TNFa production would improve colitis scoring through decreased expression of inflammatory biomarkers. Acute colitis was induced in wild type BALB/c mice using 5% dextran sulfate sodium (DSS) in drinking water for 7 days. TACE inhibition was accomplished through twice daily intraperitoneal injection of DPC- 333 (10mg/kg; BSM Inc.) To determine the effects of TACE blockade during colitis, the following experimental groups (n=6-7/group) were tested: 1) vehicle; 2) DPC-333; 3) 5% DSS and vehicle; and 4) 5% DSS and DPC-333. Twice daily TACE inhibition did not significantly improve overall colitis scoring index as determined by the presence of diarrhea, rectal bleeding, and percent weight loss. TNFa, IL-6, Il-1B, IL-10, and MPO in regional colon tissue were not reduced following DPC-333 in this model (p < 0.05). Thus, TACE inhibition does not appear to reduce colitis scoring, TNFa production, or other regional biomarkers of inflammation in this model of experimental colitis. Future studies may ascertain the role of TACE during systemic inflammatory diseases.

Copyright

© Brian Maddox

Open Access

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