Date of Graduation
Fall 2016
Degree
Master of Science in Cell and Molecular Biology
Department
Biomedical Sciences
Committee Chair
Tyler Morris
Abstract
Tumor necrosis factor a (TNFα), a potent inflammatory cytokine, has long been established as a major driving force for pathologic inflammation. Currently, anti-TNFα therapies are the standard in Inflammatory Bowel Disease (IBD) management; however, one-third of IBD patients fail to respond to anti-TNFα therapies. Previous data from this lab indicate that TNFα Converting Enzyme (TACE) inhibition does not ameliorate colitis in BALB/C mice. Thus, we hypothesized that TNFα is not a critical component in the BALB/C model of colitis. To test this, acute colitis was induced in BALB/C mice by consumption of 5% dextran sulfate sodium (DSS) in drinking water for 7 days. TACE inhibition was achieved through twice daily intraperitoneal injection of DPC-333 (10 mg/kg; BSM, Inc.) To determine the effects of TACE inhibition during colitis, BALB/C mice received the following experimental treatments: Group 1) H2O + vehicle; Group 2) DSS + vehicle; Group 3) DSS + DPC-333. Although TACE inhibition significantly reduced colon TNFα levels (p = 0.0172), no significant improvement in disease activity was observed (p = 0.74), as determined by clinical scoring of bodyweight loss, rectal bleeding, and diarrhea. Thus, colitis in BALB/C mice does not appear to be TNFα-driven and an alternative pathway must exist. It is possible that BALB/C mice could represent a pre-clinical model of primary non-responders to anti-TNFα therapies. Future studies may use this model to better understand mechanisms of primary non-response in IBD patients.
Keywords
inflammatory bowel disease, tumor necrosis factor alpha, tumor necrosis factor alpha converting enzyme, ulcerative colitis, Crohn’s disease
Subject Categories
Medical Molecular Biology
Copyright
© Carol Elaine Auterson
Recommended Citation
Biel, Stephanie E., "A Biologically Active Tnf-Alpha Inhibitor Fails To Suppress Colitis In Balb/C Mice" (2016). MSU Graduate Theses/Dissertations. 3026.
https://bearworks.missouristate.edu/theses/3026
