Article

Suppressive effect on MDC and IP-10 expression in monocytes by endocrine disruptor chemicals.

Department of Family Medicine, Zuoying Armed Force General Hospital, Kaohsiung, Taiwan, Republic of China.
Inflammation (impact factor: 1.75). 09/2009; 33(1):10-7. DOI:10.1007/s10753-009-9153-z pp.10-7
Source: PubMed

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.

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Keywords

4-octylphenol suppressed LPS-induced MDC expression
 
chemokine expression
 
CXCL10/ IFN-alpha-inducible protein 10
 
EDC-mediated signaling events
 
endocrine disrupter chemicals
 
histone H4 acetylation
 
inflammatory response
 
IP-10 expression
 
leukocyte recruitment
 
LPS-induced acetylated histone 4
 
LPS-induced activation
 
LPS-induced MDC
 
MAPK signaling pathway
 
MDC gene loci
 
MKK1/2-ERK MAPK pathway
 
monocyte-derived chemokine
 
potential impact
 
Th1 chemokine
 
Th2 chemokine
 
Th2-related chemokines
 

Ching-Hui Yeh