Apr 20th, 1:00 PM - 4:00 PM
Title
2,3,7,8-Tetrachlorodibenzo-p-dioxin Alters Interferon-Gamma Receptor and STAT-1 Levels in Mice
Faculty Sponsor
Dr. Kristen Mitchell
Information
The aryl hydrocarbon receptor (AhR) is a cytosolic ligand-activated transcription factor involved in developmental and physiological processes, including regulation of cell cycle progression. Exposure to the potent exogenous AhR agonist, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), has been shown to inhibit hepatocyte proliferation in a mouse model of liver regeneration. AhR-mediated suppression of proliferation is attributed to the Cip/ Kip family of proteins, which negatively regulate progression to S-phase of the cell cycle. One of these proteins, p21Cip1, appears to be required for the suppression of liver regeneration in mice treated with TCDD. P21Cip1 is a transcriptional target of signal transducers and activators of transcription (STAT)-1 activation, which is activated by interferon (IFN)-gamma, a cytokine that has been linked with attenuation of liver regeneration. The goal of this project was to test the hypothesis that AhR activation increases STAT-1 activation through the IFN-gamma receptor. Mice were pretreated with TCDD (20 ug/kg) or vehicle control (peanut oil) 24 hours prior to partial hepatectomy (PH), in which 70% of the liver was surgically resected. Mice were euthanized 0, 12, 24, 36, 48 and 96 hours after PH. Remnant livers were homogenized and protein content was determined. Western blotting was performed to measure protein levels of IFN-gamma receptor, STAT-1, and phosphorylated STAT-1 during liver regeneration. Preliminary results indicate altered protein levels of IFN-gamma receptor and phosphorylated STAT-1 in mice treated with TCDD compared to vehicle. Additional studies will verify this observation and to determine how exposure to TCDD alters the production of IFN-gamma during liver regeneration.