Exposure to a metabolite of the environmental toxicant, trichloroethylene, attenuates CD4+ T cell activation-induced cell death by metalloproteinase-dependent FasL shedding

Toxicological Sciences : an Official Journal of the Society of Toxicology
Sarah J Blossom, Kathleen M Gilbert

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. 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 environme...Continue Reading

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Citations

Jun 19, 2008·Environmental Health Perspectives·Glinda S CooperNoel R Rose
Jan 4, 2013·PloS One·Carolina Barragán-MartínezAdriana Rojas-Villarraga
May 30, 2009·Environmental Health Perspectives·Glinda S CooperJennifer Jinot
Oct 30, 2008·Journal of Immunotoxicology·Sarah J BlossomKathleen M Gilbert
Sep 8, 2015·International Journal of Environmental Research and Public Health·Yao PanWeidong Hao
Jan 22, 2011·Hepatitis Research and Treatment·Kathleen M Gilbert
Aug 23, 2017·Immunopharmacology and Immunotoxicology·Josue D OrdazJoseph M K Irudayaraj
Jul 25, 2018·Molecular Diagnosis & Therapy·Shannon RoseRichard E Frye

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