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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.
AuthorsErica Boldenow, Iman Hassan, Mark C Chames, Chuanwu Xi, Rita Loch-Caruso
JournalReproductive toxicology (Elmsford, N.Y.) (Reprod Toxicol) Vol. 52 Pg. 1-6 (Apr 2015) ISSN: 1873-1708 [Electronic] United States
PMID25653212 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2015 Elsevier Inc. All rights reserved.
Chemical References
  • Lipopolysaccharides
  • TNF protein, human
  • Teichoic Acids
  • Tumor Necrosis Factor-alpha
  • Trichloroethylene
  • lipoteichoic acid
  • Trichloroacetic Acid
  • S-(1,2-dichlorovinyl)cysteine
  • Cysteine
Topics
  • Chorion (immunology)
  • Cysteine (analogs & derivatives, pharmacology)
  • Decidua (immunology)
  • Disease Resistance (drug effects)
  • Extraembryonic Membranes (immunology)
  • Female
  • Humans
  • Immunity (drug effects)
  • Lipopolysaccharides (pharmacology)
  • Pregnancy
  • Streptococcal Infections (immunology)
  • Streptococcus agalactiae (immunology)
  • Teichoic Acids (pharmacology)
  • Tissue Culture Techniques
  • Trichloroacetic Acid (pharmacology)
  • Trichloroethylene (metabolism)
  • Tumor Necrosis Factor-alpha (metabolism)

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