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.
Article: Chemokine (C-C motif) ligand 22 was down-regulated in a human B lymphoblastoid cell line by PCB153 and in residents from PCBs-contaminated areas.[show abstract] [hide abstract]
ABSTRACT: Polychlorinated biphenyls (PCBs) are ubiquitous, persistent pollutants found in the environment and human tissues. Exposure to PCBs is of great concern to human health because they are known to cause neurological, reproductive, endocrinal, and other effects. The aim of the present study was to find some novel gene markers induced by PCBs through a combination of microarray screening followed by validating with quantitative real time PCR in vitro and in population investigation. In the present study, gene expression profiles of human B lymphoblastoid cells treated with different concentrations of non-coplanar 2, 2', 4, 4', 5, 5'-hexachlorobiphenyl (PCB153) were analyzed using microarray. The differentially expressed genes were further confirmed by real-time PCR in vitro and in individuals from PCBs-contaminated sites. Our results indicated an overlap of 15 differentially expressed genes among samples treated with different concentrations of PCB153, and six of them were selected for validating with qRT-PCR. Two up-regulated genes (CCDC92 and TMEM175) and three down-regulated genes (CCL22, GZMK, and STK38L) were further confirmed by qRT-PCR in vitro. The expression levels of CCL22 in individuals from PCBs-contaminated sites were significantly (P<0.05) lower than those in controls. Therefore, CCL22 seems to be a sensitive gene marker induced by PCBs, although it needs to be confirmed by further studies with a larger number of subjects.Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 01/2013; · 2.85 Impact Factor
Article: Prostaglandin I(2) analogues enhance growth-related oncogene-alpha expression in human monocyte-derived dendritic cells.[show abstract] [hide abstract]
ABSTRACT: Chemokines for neutrophils such as growth-related oncogene-alpha (GRO-alpha) are important in patients with refractory or severe asthma. Prostaglandin I(2) (PGI(2)) analogues were regarded as potential treatments for asthma. Dendritic cells (DCs) are the professional antigen-presenting cells and play a critical role in regulating immune response. However, it is unknown whether PGI(2) analogues have regulatory effects on GRO-alpha expression in human monocyte-derived DCs (MDDCs). The human MDDCs were pretreated with iloprost and treprostinil (two PGI(2) analogues) or forskolin, a cyclic adenosine monophosphate (cAMP) activator, before stimulation with lipopolysaccharide (LPS). In some cases, I prostanoid (IP) receptor and E prostanoid (EP) antagonists were pretreated before PGI(2) analogue treatment. To investigate the intracellular signaling, nuclear factor (NF)-kappaB inhibitor and the mitogen-activated protein kinase (MAPK) inhibitors were pretreated before PGI(2) analogue treatment. GRO-alpha was measured by enzyme-linked immunosorbent assay. Intracellular signaling was also investigated by Western blot. Iloprost and treprostinil enhanced LPS-induced GRO-alpha expression in MDDCs. This effect could be reversed by an I prostanoid receptor antagonist, CAY10449, but not EP receptor antagonists. Forskolin conferred a similar modulating effect as that noted in iloprost- and treprostinil-treated MDDCs. PGI(2) analogue-enhanced LPS-induced GRO-alpha expression was reduced by MAPK-p38 inhibitor, SB203580. PGI(2) analogues enhanced LPS-induced phospho-p38 expression. PGI(2) analogues enhanced LPS-induced GRO-alpha expression via the IP receptor-cAMP and p38-MAPK pathways in human MDDCs, which may further recruit neutrophil accumulation and adversely affect patients with refractory or severe asthma because of airway neutrophilia. These effects should be considered for PGI(2) analogues as candidates for the treatment of asthma.Inflammation 03/2010; 33(5):334-43. · 1.75 Impact Factor