Year of Award

2014

Document Type

Thesis

Degree Type

Master of Science (MS)

Degree Name

Cellular, Molecular and Microbial Biology

Department or School/College

Division of Biological Sciences

Committee Chair

Scott Wetzel

Commitee Members

Stephen Lodmell, David Shepherd

Keywords

regulatory T cell, immunotoxicity

Publisher

University of Montana

Abstract

Atrazine (ATR) is a chlorotriazine herbicide that is heavily used in agricultural areas. Atrazine was banned in Europe in 2006 but it is still used in the United States. It is also the most common drinking water contaminant in the United States. Atrazine has been linked to adverse health effects and displays immunotoxicity. It is a potent phosphodiesterase inhibitor and has been shown to induce aromatase activity leading to elevated estrogen levels. Previous studies demonstrated that in vitro atrazine exposure inhibits CD4+ T cell activation and proliferation and increases the frequency of Foxp3+ CD4+ T cells with more severe phenotypes in male-derived cells. The decreased proliferation and activation of CD4+ T cells was not replicable by pharmacologically increasing cAMP. This, along with the sex bias, suggested that ATR elevation of estrogen could mediate an increased severity in T cell proliferation and activation, specifically through GPER-1. We show that treatment with the GPER-1 agonist G-1 can mimic effects seen with low concentrations of ATR but blockade of GPER-1 with the antagonist G-36 does not alleviate ATR-mediated effects on CD4+ T cells. We also show that estrogen can synergize with ATR to further decrease CD4+ T cell proliferation and activation upon challenge with antigen. Overall, GPER-1 does not appear to be involved in the ATR mediated decrease in CD4+ T cell proliferation, activation, or increase in the frequency of Foxp3+ Tregs in vitro.

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© Copyright 2014 Tiffany Emmons