title: The trichloroethylene metabolite S-(1,2-dichlorovinyl)-l-cysteine but not trichloroacetate inhibits pathogen-stimulated TNF-α in human extraplacental membranes in vitro.
abstract: Extraplacental membranes define the gestational compartment and provide a barrier to infectious microorganisms ascending the gravid female reproductive tract. We tested the hypothesis that bioactive metabolites of trichloroethylene (TCE) decrease pathogen-stimulated innate immune response of extraplacental membranes. Extraplacental membranes were cultured for 4, 8, and 24h with the TCE metabolites trichloroacetate (TCA) or S-(1,2-dichlorovinyl)-l-cysteine (DCVC) in the absence or presence of lipoteichoic acid (LTA) or lipopolysaccharide (LPS) to simulate infection. In addition, membranes were cocultured with DCVC and Group B Streptococcus (GBS). DCVC (5-50μM) significantly inhibited LTA-, LPS-, and GBS-stimulated cytokine release from tissue cultures as early as 4h (P≤0.05). In contrast, TCA (up to 500μM) did not inhibit LTA-stimulated cytokine release from tissue punches. Because cytokines are important mediators for host response to infectious microorganisms these findings suggest that TCE exposure could potentially modify susceptibility to infection during pregnancy.
authors: Department of Environmental Health Sciences, School of Public Health, University of Michigan, 1415 Washington Heights, Ann Arbor, MI 48109-2029, USA. Electronic address: boldenow@umich.edu.
authors: Erica
authors: E
authors: Boldenow
authors: Department of Environmental Health Sciences, School of Public Health, University of Michigan, 1415 Washington Heights, Ann Arbor, MI 48109-2029, USA. Electronic address: ihass@umich.edu.
authors: Iman
authors: I
authors: Hassan
authors: Departments of Pathology and of Obstetrics and Gynecology, Medical School, University of Michigan, 4215 Med Sci I SPC 5602, Ann Arbor, MI 48109-5602, USA. Electronic address: mchames@med.umich.edu.
authors: Mark C
authors: MC
authors: Chames
authors: Department of Environmental Health Sciences, School of Public Health, University of Michigan, 1415 Washington Heights, Ann Arbor, MI 48109-2029, USA. Electronic address: cxi@umich.edu.
authors: Chuanwu
authors: C
authors: Xi
authors: Department of Environmental Health Sciences, School of Public Health, University of Michigan, 1415 Washington Heights, Ann Arbor, MI 48109-2029, USA. Electronic address: rlc@umich.edu.
authors: Rita
authors: R
authors: Loch-Caruso
mesh_terms: D002823:Chorion / Q000276:immunology; D003545:Cysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D003656:Decidua / Q000276:immunology; D060467:Disease Resistance / Q000187:drug effects; D005321:Extraembryonic Membranes / Q000276:immunology*; D005260:Female; D006801:Humans; D007109:Immunity / Q000187:drug effects*; D008070:Lipopolysaccharides / Q000494:pharmacology; D011247:Pregnancy; D013290:Streptococcal Infections / Q000276:immunology; D013292:Streptococcus agalactiae / Q000276:immunology*; D013682:Teichoic Acids / Q000494:pharmacology; D046509:Tissue Culture Techniques; D014238:Trichloroacetic Acid / Q000494:pharmacology*; D014241:Trichloroethylene / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D008070:Lipopolysaccharides; C439524:TNF protein, human; D013682:Teichoic Acids; D014409:Tumor Necrosis Factor-alpha; D014241:Trichloroethylene; C009900:lipoteichoic acid; D014238:Trichloroacetic Acid; C039961:S-(1,2-dichlorovinyl)cysteine; D003545:Cysteine
keywords: Dichlorovinyl cysteine; Group B Streptococcus; Pregnancy; Toxicant–pathogen interactions; Trichloroethylene
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