國家衛生研究院 NHRI:Item 3990099045/15247
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    題名: Maternal di-(2-ethylhexyl) phthalate exposure elicits offspring IFN-λ upregulation: Insights from birth cohort, murine model, and in vitro mechanistic analysis
    其他題名: Maternal di-(2-ethylhexyl) phthalate exposure elicits offspring IFN-lambda upregulation: Insights from birth cohort, murine model, and in vitro mechanistic analysis
    作者: Kuo, FC;Tsai, ML;Wu, ST;Li, SS;Wu, CF;Wang, SL;Chan, MWY;Suen, JL;Wu, MT;Hung, CH
    貢獻者: National Institute of Environmental Health Sciences
    摘要: Maternal exposure to di-(2-ethylhexyl)-phthalate (DEHP), an environmental endocrine disruptor, may lead to developmental immunotoxicity in offspring. The causal relationship and underlying mechanism require further study. A subset of Taiwan Maternal and Infant Cohort Study data (n = 283) was analyzed and found a significant association between urinary DEHP metabolite levels from the third trimester of pregnancy and plasma levels of IL-28 A and IL-29, named IFNλs, in cord blood. A trans-maternal murine model mimicking human DEHP exposure way showed that bone marrow-derived dendritic cells from maternal DEHP-exposed F1 offspring secreted higher IL-28 A levels than control cells, indicating a potential causal relationship. Human bronchial epithelial cell lines treated with DEHP or its primary metabolite, mono-(-2ethyl-5-hexyl) phthalate (MEHP), expressed significantly higher levels of IFNλs mRNA or protein than controls. MEHP's effect on IFNλs expression was blocked by peroxisome proliferator-activated receptor α (PPAR-α) and PPAR-γ antagonists, and inhibited by a histone acetyltransferase inhibitor or a histone methyltransferase inhibitor. Chromatin immunoprecipitation assay showed that MEHP treatment promoted histone modifications at H3 and H4 proteins at the promoter regions of Il28a and Il29 genes. These results suggest maternal DEHP exposure could result in high IFNλ expression in offspring, and the health risk of early-life exposure requires further investigation.
    日期: 2023-08-21
    關聯: Food and Chemical Toxicology. 2023 Aug 21;179:Article number 113993.
    Link to: http://dx.doi.org/10.1016/j.fct.2023.113993
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0278-6915&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:001085018500001
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85169847135
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