Suppressive Effect on MDC and IP-10 Expression in Monocytes by Endocrine Disruptor Chemicals
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Suppressive Effect on MDC and IP-10 Expression in Monocytes by Endocrine Disruptor Chemicals Ching-Hui Yeh,1,2 Hsaing-Chi Wu,1 Thai-Hung Kuo,1 Chang-Hung Kuo,3 San-Nan Yang,3,4,5 Wei-Li Wang,3 Huan-Nan Chen,6 Wan-Ju Wei,6 and Chih-Hsing Hung3,4,5,6,7
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-α-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. KEY WORDS: endocrine disruptor chemical; MDC; IP-10; monocyte; chemokine.
INTRODUCTION
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Department of Family Medicine, Zuoying Armed Force General Hospital, Kaohsiung, Taiwan, Republic of China 2 Department of Business Management, National Sun Yat-Sen University, Kaohsiung, Taiwan, Republic of China 3 Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan, Republic of China 4 Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, Republic of China 5 Department of Pediatrics, Faculty of Pediatrics, College of Medicine, Kaohsiung, Taiwan, Republic of China 6 Center of Excellence for Environmental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, Republic of China 7 To whom correspondence should be addressed at Department of Pediatrics, Kaohsiung Medical University Hospital, #100, Tz-You 1st Road, Kaohsiung 807, Kaohsiung, Taiwan, Republic of China. E-mail: [email protected]
Polarization with cytokines influences every aspect of the immune response from the innate to the adaptive. For monocytes, cytokines influence the production of chemokines, the expression of costimulato
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