2. Academic Validation
  3. The trichloroethylene metabolite S-(1,2-dichlorovinyl)-l-cysteine but not trichloroacetate inhibits pathogen-stimulated TNF-α in human extraplacental membranes in vitro

The trichloroethylene metabolite S-(1,2-dichlorovinyl)-l-cysteine but not trichloroacetate inhibits pathogen-stimulated TNF-α in human extraplacental membranes in vitro

  • Reprod Toxicol. 2015 Apr;52:1-6. doi: 10.1016/j.reprotox.2015.01.007.
Erica Boldenow 1,  Iman Hassan 2,  Mark C Chames 3,  Chuanwu Xi 4,  Rita Loch-Caruso 5
Affiliations

Affiliations

  • 1 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.
  • 2 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.
  • 3 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.
  • 4 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.
  • 5 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.
PMID: 25653212 DOI: 10.1016/j.reprotox.2015.01.007
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.

Keywords

Dichlorovinyl cysteine; Group B Streptococcus; Pregnancy; Toxicant–pathogen interactions; Trichloroethylene.

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