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ToxSci Advance Access published online on October 31, 2006
Toxicological Sciences, doi:10.1093/toxsci/kfl149
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© 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 July 20, 2006
Accepted October 9, 2006

Immunotoxiocology

Chronic Exposure to a Trichloroethylene Metabolite in Autoimmune-Prone MRL+/+ Mice Promotes Immune Modulation and Alopecia

Sarah J. Blossom 1 *, Jason C. Doss 2, and Kathleen M. Gilbert 3

1 Department of Pediatrics, College of Medicine, University of Arkansas for Medical Sciences/Arkansas Children's Hospital Research Institute, 1120 Marshall St, Little Rock, AR 72202 USA
2 Department of Pathology, College of medicine, University of Arkansas for Medical Sciences, 4301 W. Markham, Little Rock, AR 72205 USA
3 Department of Microbiology and Immunology, College of Medicine, 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

The industrial solvent trichloroethylene (TCE) is a widespread environmental contaminant known to impact the immune system. In the present study, female MRL+/+ mice were treated for 40 weeks with trichloroacetaldehyde hydrate (TCAH), a metabolite of TCE, in the drinking water. The results were compared with the data from an earlier study in which MRL+/+ mice were exposed to TCAH for 4 weeks. Following a 40 week exposure, the mice developed skin inflammation and dose-dependent alopecia. In addition, TCAH appeared to modulate the CD4+ T cell subset by promoting the expression of an activated/effector (i.e., CD62Llo) phenotype with an increased capacity to secrete the proinflammatory cytokine IFN-{gamma}. However, unlike what was observed after only 4 weeks of exposure, TCAH did not significantly attenuate activation-induced-cell death (AICD) or the expression of the death receptor, FasL, in CD4+ T cells. Some metalloproteinases (MMPs) are thought to play a role in susceptibility to AICD by inducing FasL shedding. Thus, both the 4 and 40 week sera were tested for MMP-7 levels in an attempt to explain the disparate results of TCAH on AICD and FasL expression. Serum MMP-7 levels were significantly higher in mice exposed to TCAH for 4 weeks. In contrast, the serum MMP-7 levels were increased in all of the mice by 40 weeks when compared to a non-autoimmune strain. Taken together, a chronic exposure to TCAH promotes alopecia and skin inflammation. The early effects of TCAH on MMP-7 levels may provide a mechanism by which TCAH promotes skin pathology.

Keywords: TCAH; rodent; CD4+ T cell; alopecia.
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