title: 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) enhances placental inflammation.
abstract: Preterm birth is a leading cause of perinatal morbidity and mortality that is often associated with ascending infections from the lower genital tract. Recent studies with animal models have suggested that developmental exposure to the environmental toxin 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) can increase the risk of preterm birth in the offspring. How TCDD may modify placental immunity to ascending infections is unclear. Therefore, we studied the effects of TCDD treatment on basal and Escherichia coli-stimulated cytokine production by placental explants. Cultures of second-trimester placentas were treated with up to 40 nM TCDD for 72 h and then stimulated with 10(7)CFU/ml E. coli for an additional 24h. Concentrations of cytokines and PGE2 were measured in conditioned medium by immunoassay. TCDD exposure increased mRNA levels of IL-1β by unstimulated cultures, but no effects on protein levels of this cytokine were detected. TNF-α production was unaffected by TCDD for unstimulated cultures, but pre-treatment with 40 nM TCDD significantly increased E. coli-stimulated TNF-α production. Both basal and bacteria-stimulated PGE2 and COX-2 gene expression were enhanced by TCDD pretreatment. In contrast, production of the anti-inflammatory cytokine, IL-10, was reduced by TCDD pretreatment for both unstimulated and E. coli-stimulated cultures. No effect of TCDD on the viability of the cultures was detected. These results suggest that TCDD exposure may shift immunity to enhance a proinflammatory phenotype at the maternal-fetal interface that could increase the risk of infection-mediated preterm birth.
authors: Women and Children's Health Research Laboratory, Winthrop University Hospital, Mineola, NY, USA.
authors: Morgan R
authors: MR
authors: Peltier
authors: Yuko
authors: Y
authors: Arita
authors: Natalia G
authors: NG
authors: Klimova
authors: Ellen M
authors: EM
authors: Gurzenda
authors: Hchi-Chi
authors: HC
authors: Koo
authors: Amitasrigowri
authors: A
authors: Murthy
authors: Veronica
authors: V
authors: Lerner
authors: Nazeeh
authors: N
authors: Hanna
mesh_terms: D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D004781:Environmental Exposure; D004785:Environmental Pollutants / Q000633:toxicity*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007249:Inflammation / Q000139:chemically induced* / Q000276:immunology; D018836:Inflammation Mediators / Q000378:metabolism; D010920:Placenta / Q000187:drug effects* / Q000276:immunology; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D011247:Pregnancy; D047928:Premature Birth / Q000139:chemically induced* / Q000276:immunology
chemical_list: D016207:Cytokines; D004785:Environmental Pollutants; D018836:Inflammation Mediators; D000072317:Polychlorinated Dibenzodioxins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D015232:Dinoprostone
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