Skip Navigation



ToxSci Advance Access published online on April 26, 2006
Toxicological Sciences, doi:10.1093/toxsci/kfj212
This Article
Right arrow Advance Access manuscript (PDF) Freely available
Right arrow All Versions of this Article:
92/1/103    most recent
kfj212v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Blossom, S. J.
Right arrow Articles by Gilbert, K. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Blossom, S. J.
Right arrow Articles by Gilbert, K. M.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2006. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Received February 17, 2006
Accepted April 7, 2006

Immunotoxiocology

Exposure to a Metabolite of the Environmental Toxicant, Trichloroethylene, Attenuates CD4+ T Cell Activation-induced Cell Death by Metalloproteinase-Dependent FasL Shedding

Sarah J. Blossom 1 * and Kathleen M. Gilbert 1

1 Department of Microbiology and Immunology, University of Arkansas for Medical Sciences/Arkansas Children's Hospital Research Institute, 1120 Marshall St, Little Rock, AR 72202 USA

* To whom correspondence should be addressed.
Sarah J. Blossom, E-mail: blossomsarah{at}uams.edu


  Abstract

Long-term exposure to the environmental contaminant, trichloroethylene (TCE) in drinking water has been shown to promote autoimmune disease in association with the expansion of activated CD4+ T cells. The effects of TCE on CD4+ T cells were linked in the present study to the ability of TCE metabolite, trichloroacetaldehyde hydrate (TCAH), to inhibit activation-induced cell death (AICD) in CD4+ T cells. TCAH attenuated AICD in CD4+ T cells by decreasing FasL (CD178) expression, but not by altering Fas (CD95) expression or by interfering with Fas signaling events following direct engagement of the Fas receptor. The TCAH-induced decrease in FasL expression did not appear to be mediated at the transcriptional level, but was instead due to increased shedding of FasL from the surface of the CD4+ T cells. The ability of TCAH to cleave FasL and thereby decrease AICD appeared to be mediated by metalloproteinases, and correlated with a TCAH-induced increase in matrix metalloproteinase-7 (MMP-7). Thus, this study presents the novel finding that the environmental contaminant TCE works via its metabolite TCAH to attenuate AICD by increasing metalloproteinase activity that cleaves FasL from CD4+ T cells. This represents a mechanism by which an environmental trigger inhibits AICD in CD4+ T cells, and may thereby promote CD4+ T cell-mediated autoimmune disease.

Keywords: apoptosis; autoimmunity; T cells; metalloproteinase; trichloroethylene.
Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Toxicol SciHome page
S. J. Blossom, J. C. Doss, and K. M. Gilbert
Chronic Exposure to a Trichloroethylene Metabolite in Autoimmune-Prone MRL+/+ Mice Promotes Immune Modulation and Alopecia
Toxicol. Sci., February 1, 2007; 95(2): 401 - 411.
[Abstract] [Full Text] [PDF]


Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.