ToxSci Advance Access originally published online on October 31, 2006
Toxicological Sciences 2007 95(2):401-411; doi:10.1093/toxsci/kfl149
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Chronic Exposure to a Trichloroethylene Metabolite in Autoimmune-Prone MRL+/+ Mice Promotes Immune Modulation and Alopecia
* Department of Pediatrics, College of Medicine, University of Arkansas for Medical Sciences/Arkansas Children's Hospital Research Institute, Little Rock, Arkansas 72202
Department of Pathology, College of medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205
Department of Microbiology and Immunology, College of Medicine, University of Arkansas for Medical Sciences/Arkansas Children's Hospital Research Institute, Little Rock, Arkansas 72202
1 To whom correspondence should be addressed at Arkansas Children's Hospital Research Institute, Little Rock, AR 72202. Fax: (501) 364-3599. E-mail: blossomsarah{at}uams.edu.
Received July 20, 2006; accepted October 9, 2006
 |
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 interferon-
. 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 the mice by 40 weeks when compared with a nonautoimmune 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.
Key Words: TCAH; rodent; CD4+ T cell; alopecia.