title: Suppressive effect on MDC and IP-10 expression in monocytes by endocrine disruptor chemicals.
abstract: The expression of chemokines is critical in leukocyte recruitment and inflammation, but the regulatory mechanisms involved remain incompletely defined. While endocrine disrupter chemicals (EDCs) are known to be ubiquitous in the environment and often associated with altered inflammatory response, their potential impact on chemokine expression in monocytes is at present unknown. To this end, the effects of EDCs on the expression of Th1- and Th2-related chemokines in a human monocytic cell line, THP-1, were investigated. THP-1 cells were pre-treated with varying concentrations of EDCs (nonylphenol and 4-octylphenol) with or without the addition of an estrogen receptor (ER) antagonist, ICI 182,780 and then stimulated by lipopolysaccharide (LPS). The levels of chemokines, CXCL10/ IFN-alpha-inducible protein 10 (IP-10, a Th1 chemokine) and monocyte-derived chemokine (MDC)/CCL22, a Th2 chemokine) were measured by ELISA. EDC-mediated signaling events and histone modifications were examined by the use of Western blotting and chromatin immunoprecipitation (ChIP) assay. Nonylphenol and 4-octylphenol were able to suppress LPS-induced MDC and IP-10 expression. This suppressive effect was not reversed by the addition of ICI 182,780. Nonylphenol and 4-octylphenol reduced LPS-induced activation of MAPK signaling pathway, MKK1/2 and ERK, concomitant with decreased levels of LPS-induced acetylated histone 4 (H4) at the IP-10 and MDC gene loci. Nonylphenol and 4-octylphenol suppressed LPS-induced MDC expression in monocytes via, at least in part, the MKK1/2-ERK MAPK pathway and histone H4 acetylation, but not the estrogen receptor.
authors.affiliation: Department of Family Medicine, Zuoying Armed Force General Hospital, Kaohsiung, Taiwan, Republic of China.
authors.forename: Ching-Hui
authors.initials: CH
authors.lastname: Yeh
authors.forename: Hsaing-Chi
authors.initials: HC
authors.lastname: Wu
authors.forename: Thai-Hung
authors.initials: TH
authors.lastname: Kuo
authors.forename: Chang-Hung
authors.initials: CH
authors.lastname: Kuo
authors.forename: San-Nan
authors.initials: SN
authors.lastname: Yang
authors.forename: Wei-Li
authors.initials: WL
authors.lastname: Wang
authors.forename: Huan-Nan
authors.initials: HN
authors.lastname: Chen
authors.forename: Wan-Ju
authors.initials: WJ
authors.lastname: Wei
authors.forename: Chih-Hsing
authors.initials: CH
authors.lastname: Hung
mesh_terms: D000107:Acetylation; D015153:Blotting, Western; D002460:Cell Line; D054422:Chemokine CCL22 / Q000235:genetics / Q000378:metabolism*; D054357:Chemokine CXCL10 / Q000235:genetics / Q000378:metabolism*; D047369:Chromatin Immunoprecipitation; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D052244:Endocrine Disruptors / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D000077267:Fulvestrant; D006657:Histones / Q000378:metabolism; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D048369:MAP Kinase Kinase 1 / Q000378:metabolism; D048370:MAP Kinase Kinase 2 / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology; D010636:Phenols / Q000494:pharmacology*; D011401:Promoter Regions, Genetic; D015398:Signal Transduction / Q000187:drug effects
chemical_list: C515482:CCL22 protein, human; C114753:CXCL10 protein, human; D054422:Chemokine CCL22; D054357:Chemokine CXCL10; D052244:Endocrine Disruptors; D004965:Estrogen Antagonists; D006657:Histones; D008070:Lipopolysaccharides; D010636:Phenols; D000077267:Fulvestrant; D004958:Estradiol; C025256:nonylphenol; C080417:4-octylphenol; C482128:MAP2K2 protein, human; D048049:Extracellular Signal-Regulated MAP Kinases; D048369:MAP Kinase Kinase 1; D048370:MAP Kinase Kinase 2; C482125:MAP2K1 protein, human