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Undergraduate Research Project Management System

A Cellular Model for Modulation of the Immune Regulator RANTES by Environmental Contaminates

Status Complete
Seeking Researchers No
Start Date 09/01/2003
End Date 06/30/2004
Funding Source Undergraduate Research Grants
Funding Amount
Community Partner
Related Course
Last Updated 07/05/2008 01:25AM
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Faculty
  Carol Jones

Student Researchers
  Carmen Hanson

Abstract

Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a serious occurrence in the Arctic regions of Alaska . This contaminant has been associated with inflammatory diseases, and is potentially carcinogenic. TCDD mediates its responses in the human body through interactions with the aryl hydrocarbon receptor (AhR). Once bound by dioxin, this receptor becomes a transcription factor that alters gene expression. Exposure to TCDD has also been shown to stimulate the chemokine RANTES (regulated upon activation, normal T-cell expressed and secreted) in several human cell models. RANTES attracts circulating mononuclear cells such as monocytes, lymphocytes, and eosinphils, and evidence suggests a role for RANTES in the progression of some viral diseases and inflammatory disorders, such as asthma. RANTES is a natural ligand for the CCR5 receptor, which functions as a co-receptor for the human immunodeficiency virus (HIV). It has been shown that the level of the CCR5 receptor present in the cell is an important factor in determining the rate of HIV infection. Many cell types express RANTES, including endothelial cells, T cells, lung epithelial cells and airway smooth muscle cells. Based on this evidence, the human lung adenocarcinoma cell line, A549, will be treated with TCDD, and the levels of RANTES will be measured. A549 is known to express the Ah receptor, and increases in CYP1A1 gene activity following TCDD exposure have been documented. Following determination of the level of RANTES, the treated cells will be examined for the level and location of the CCR5 receptor. It is hypothesized that the TCDD will stimulate RANTES, which will in turn upregulate the CCR5 receptor levels in these cells. This exposure could also affect the location of the CCR5 receptor in the plasma membrane of the cell. The increased receptor load could potentially render human populations exposed to TCDD and related environmental contaminants more susceptible to viral infection by viruses such as HIV, which enter their hosts using the CCR5 receptor

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