Date of Graduation
Master of Science in Cell and Molecular Biology
TNFa, converting enzyme, colitis, inflammation
Medical Molecular Biology
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.
© Brian Maddox
Maddox, Brian, "Tumor Necrosis Factor Alpha Converting Enzyme Inhibition during Acute Colitis in Mice: A Regional Analysis" (2015). MSU Graduate Theses. 2866.