title: Chronic exposure to a trichloroethylene metabolite in autoimmune-prone MRL+/+ mice promotes immune modulation and alopecia.
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., CD62L(lo)) phenotype with an increased capacity to secrete the proinflammatory cytokine interferon-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 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.
authors.affiliation: Department of Pediatrics, College of Medicine, University of Arkansas for Medical Sciences/Arkansas Children's Hospital Research Institute, Little Rock, Arkansas 72202, USA. blossomsarah@uams.edu
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Blossom
authors.forename: Jason C
authors.initials: JC
authors.lastname: Doss
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Gilbert
mesh_terms: D000284:Administration, Oral; D000505:Alopecia / Q000139:chemically induced* / Q000276:immunology / Q000473:pathology; D000818:Animals; D001327:Autoimmune Diseases / Q000139:chemically induced* / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002697:Chloral Hydrate / Q000031:analogs & derivatives* / Q000378:metabolism / Q000633:toxicity; D003872:Dermatitis / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000378:metabolism / Q000633:toxicity*; D053222:Fas Ligand Protein / Q000276:immunology; D005260:Female; D007371:Interferon-gamma / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D020783:Matrix Metalloproteinase 7 / Q000378:metabolism; D051379:Mice; D019463:Mice, Inbred MRL lpr; D013154:Spleen / Q000187:drug effects / Q000276:immunology; D013997:Time Factors; D014241:Trichloroethylene / Q000378:metabolism / Q000633:toxicity*
chemical_list: D004785:Environmental Pollutants; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D014241:Trichloroethylene; D002697:Chloral Hydrate; D007371:Interferon-gamma; D020783:Matrix Metalloproteinase 7; C021100:trichloroacetaldehyde