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Publication Date
12-2014
Date of Final Oral Examination (Defense)
10-23-2014
Type of Culminating Activity
Thesis - Boise State University Access Only
Degree Title
Master of Science in Biology
Department
Biology
Supervisory Committee Chair
Kristen A. Mitchell, Ph.D.
Supervisory Committee Member
Kenneth A. Cornell, Ph.D.
Supervisory Committee Member
Cheryl Jorcyk, Ph.D.
Supervisory Committee Member
Troy Rohn, Ph.D.
Abstract
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is an environmental pollutant in the family of halogenated aromatic hydrocarbons. Exposure to TCDD elicits a spectrum of toxic effects, many of which are rooted in aberrant cell proliferation, activation, and differentiation. The liver is a target organ for TCDD toxicity, yet the mechanisms of toxicity remain unclear. In the present study, we tested the hypothesis that TCDD treatment enhances activation of hepatic stellate cells (HSCs), which are non-parenchymal cells in the liver that are involved in vitamin A storage and wound healing processes. We used a recently established human HSC line, LX-2, to determine how TCDD treatment affects proliferation, cytokine production, collagen production, and vitamin A storage. Results indicate that TCDD treatment increased LX-2 cell proliferation and production of monocyte chemoattractant protein (MCP)-1, yet had no effect on the production of transforming growth factor-β1 or collagen type I. TCDD treatment completely abolished vitamin A storage in LX-2 cells. When PI3 kinase and PKC signaling pathways were inhibited, TCDD treatment failed to increase proliferation but still enhanced MCP-1 production. These results support the notion that HSCs may be directly targeted during TCDD exposure. Furthermore, TCDD treatment appears to increase HSC activation through multiple distinct cell signaling pathways. Finally, these findings provide a rationale for future studies investigating the role of dysregulated HSC function during TCDD-induced hepatotoxicity.
Recommended Citation
Harvey, Wendy Amanda, "Consequences of 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) on Hepatic Stellate Cell Activation In Vitro" (2014). Boise State University Theses and Dissertations. 885.
https://scholarworks.boisestate.edu/td/885