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 24 h 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 (5-50 μM) significantly inhibited LTA-, LPS-, and GBS-stimulated cytokine release from tissue punch cultures as early as 4 h (p ≤ 0.05). In contrast, TCA (up to 500 μM) 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.

Group B Streptococcal Maternal Colonization and Neonatal Disease: Molecular Mechanisms and Preventative Approaches

“…Ascension of GBS from the vaginal tract has been observed in both non-pregnant ( 62 ) and pregnant mice ( 172 ) suggesting this is the main route by which GBS compromises placental tissues. GBS stimulates HBD-2, IL-1β, IL-8, IL-10, and TNF-α in human extraplacental or chorioamniotic membranes ex vivo ( 103 , 173 – 175 ). In a rhesus monkey GBS infection model, increased amniotic fluid TNF-α, IL-1β, and IL-6 occurred before uterine contractility or any clinical signs of infection, suggesting a direct role for infection in triggering preterm labor ( 176 ).…”

Group B streptococcus activates transcriptomic pathways related to premature birth in human extraplacental membranes in vitro†,‡

“…Gestational tissues stimulated with GBS produce unique inflammatory cytokine profiles. We previously reported that GBS inoculation ex vivo stimulated secretion of proinflammatory cytokines such as IL1A, IL1B, TNF, and CXCL8 (IL8) from human extraplacental membranes in transwell cultures and from human extraplacental membranes dissected free of amnion [18,19]. Other studies reported similar results, showing that GBS stimulated IL1B, IL6, IL10, and TNF release from human extraplacental membranes [20][21][22].…”

“…such as interleukins, tumor necrosis factor, and granulocyte colonystimulating factors [33]. Indeed, multiple studies have reported that GBS stimulates the release of inflammatory cytokines from human extraplacental membranes [18,19,21,22,34]. These cytokines stimulate gestational tissues to produce PGs such as PGE2 and PGF2A [35].…”

Perinatal Group B Streptococcal Infections: Virulence Factors, Immunity, and Prevention Strategies

“…GBS are able to adhere to and invade both chorionic and amniotic epithelial cells [62, 91], which are partially mediated by several factors: 1) IagA, a glycosyltransferase that helps anchor lipoteichoic acid to the cell surface [92], 2) the hemolytic pigment and its regulator CovR/S [62], and 3) quorum sensing mediated by genes in the rgf operon [93]. GBS has also been shown to induce secretion of multiple cytokines and defensins from placental membranes ex vivo , including TNF-α, IL-1α, IL-1β, IL-6, and IL-8 [44, 62, 94–96]. Inflammation is stimulated either through pattern-recognition receptor (PRR) sensing of GBS antigens [44, 94] or by pigment-mediated activation of nuclear factor-κB (NF-κB) [62].…”

“…GBS has also been shown to induce secretion of multiple cytokines and defensins from placental membranes ex vivo , including TNF-α, IL-1α, IL-1β, IL-6, and IL-8 [44, 62, 94–96]. Inflammation is stimulated either through pattern-recognition receptor (PRR) sensing of GBS antigens [44, 94] or by pigment-mediated activation of nuclear factor-κB (NF-κB) [62]. An important family of PRRs that mediates placental membrane immunity are the Siglecs [97, 98], a family of cell-surface sialic acid binding lectins that regulate innate and adaptive immune function [99].…”