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Small Organic Molecule Inhibition of Tumor Necrosis Factor-a Induced Vascular Cell Adhesion Molecule-1 Expression by Endothelial Cells

Alapati, Anuja

Abstract Details

2013, Master of Science (MS), Ohio University, Biomedical Engineering (Engineering and Technology).
Suppressing aberrant endothelial cell adhesion molecule (ECAM) expression, which plays a critical role in leukocyte adhesion and thus pathological inflammation, is a promising therapeutic approach to treat inflammatory disease. The ECAMs, in particular vascular cell adhesion moleule-1 (VCAM-1), are up regulated by pro-inflammatory cytokines, e.g. tumor necrosis factor- a (TNF-a), during inflammation. VCAM-1 is considered a crucial molecule for inhibition as it is involved in many inflammatory diseases including atherosclerosis, arthritis, and colitis. Several studies report that subtle modifications in a compound’s structure can significantly increase the compound’s activity and toxicity. In this study, we compared the ability of several small organic compounds to inhibit TNF-a induced VCAM-1 expression by human umbilical vein endothelial cells (HUVECs) using an enzyme-linked immunosorbent assay (ELISA). In parallel, the compounds’ effects on HUVEC viability was studied using an MTS assay. The MTS assay is a measure of metabolic activity and thus can correlate with cell viability. After obtaining the inhibition and toxicity levels of the compounds, the “therapeutic indices” were determined. The therapeutic index gives insight into the compound’s potency relative to its toxicity. Combined, these studies provide insights into the structure-activity relationships for small organic compound inhibition of TNF-a induced VCAM-1 expression by HUVECs.
Douglas Goetz, PhD (Advisor)
Monica Burdick, PhD (Committee Member)
Fabian Benencia, PhD (Committee Member)
Stephen Bergmeier, PhD (Committee Member)
43 p.

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Citations

  • Alapati, A. (2013). Small Organic Molecule Inhibition of Tumor Necrosis Factor-a Induced Vascular Cell Adhesion Molecule-1 Expression by Endothelial Cells [Master's thesis, Ohio University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1375177527

    APA Style (7th edition)

  • Alapati, Anuja. Small Organic Molecule Inhibition of Tumor Necrosis Factor-a Induced Vascular Cell Adhesion Molecule-1 Expression by Endothelial Cells . 2013. Ohio University, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1375177527.

    MLA Style (8th edition)

  • Alapati, Anuja. "Small Organic Molecule Inhibition of Tumor Necrosis Factor-a Induced Vascular Cell Adhesion Molecule-1 Expression by Endothelial Cells ." Master's thesis, Ohio University, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1375177527

    Chicago Manual of Style (17th edition)