國家衛生研究院 NHRI:Item 3990099045/14363
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    题名: Di-(2-ethylhexyl) phthalate promotes allergic lung inflammation by modulating CD8a(+) dendritic cell differentiation via metabolite MEHP-PPARgamma axis
    其它题名: Di-(2-ethylhexyl) phthalate promotes allergic lung inflammation by modulating CD8a(+) dendritic cell differentiation via metabolite MEHP-PPARγ axis
    作者: Tseng, HH;Li, CY;Wu, ST;Su, HH;Wong, TH;Wu, HE;Chang, YW;Huang, SK;Tsai, EM;Suen, JL
    贡献者: National Institute of Environmental Health Sciences
    摘要: Di-(2-ethylhexyl) phthalate (DEHP), a common plasticizer, is a ubiquitous environmental pollutant that can disrupt endocrine function. Epidemiological studies suggest that chronic exposure to DEHP in the environment is associated with the prevalence of childhood allergic diseases; however, the underlying causal relationship and immunological mechanism remain unclear. This study explored the immunomodulatory effect of DEHP on allergic lung inflammation, while particularly focusing on the impact of DEHP and its metabolite on dendritic cell differentiation and activity of peroxisome proliferator-activated receptor gamma (PPAR gamma). The results showed that exposure to DEHP at a human tolerable daily intake dose exacerbated allergic lung inflammation in mice. Ex vivo flow cytometric analysis revealed that DEHP-exposed mice displayed a significantly decreased number of CD8 alpha(+) dendritic cells (DCs) in spleens and DC progenitors in the bone marrow, as well as, less interleukin-12 production in splenic DCs and increased T helper 2 polarization. Pharmacological experiments showed that mono-(2-ethylhexyl) phthalate (MEHP), the main metabolite of DEHP, significantly hampered the differentiation of CD8 alpha(+) DCs from Fms-like tyrosine kinase 3 ligand-differentiated bone marrow culture, by modulating PPAR gamma activity. These results suggested that chronic exposure to DEHP at environmentally relevant levels, promotes allergic lung inflammation, at least in part, by altering DC differentiation through the MEHP-PPAR gamma axis. This study has crucial implications for the interaction(s) between environmental pollutants and innate immunity, with respect to the development of allergic asthma.
    日期: 2022-05-19
    關聯: Frontiers in Immunology. 2022 May 19;13:Article number 581854.
    Link to: http://dx.doi.org/10.3389/fimmu.2022.581854
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1664-3224&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000806558800001
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85131346341
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