Di-(2-ethylhexyl) phthalate induces production of inflammatory molecules in human macrophages
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Objective and design
To investigate whether di-(2-ethylhexyl) phthalate (DEHP) affects the production of inflammatory cytokines by human macrophages.
Materials and methods
Differentiated macrophage-like THP-1 cells were exposed to 200 μM DEHP for 3 h, followed by incubation in the presence or absence of opsonized zymosan A, and the concentrations of TNF-α, IL-1β, IL-8, and IL-6 in the culture media were determined by ELISA. DNA microarray and quantitative real-time RT-PCR analyses were performed to identify genes that showed changes in expression in response to DEHP.
DEHP treatment increased the concentrations of TNF-α, IL-1β, IL-8, and IL-6 in the media, regardless of whether the cells phagocytosed zymosan. DNA microarray analysis showed that DEHP increased the levels of expression of IL-8, CXCL1, CXCL2, CXCL3, CXCL6, CCL3, MMP3, MMP10, MMP14, and CSF2 mRNA, and real-time RT-PCR showed that DEHP significantly enhanced the levels of expression of IL-8, CXCL1, CXCL2, CXCL3, CXCL6, CCL3, MMP10, CSF2, TNF-α, IL-1β, and IL-6 mRNA in THP-1 cells. DEHP significantly induced translocation of p65 NF-κB into the nucleus.
DEHP enhances the production of inflammatory cytokines and chemokines by macrophages, and exacerbates their inflammatory response.
KeywordsDi-(2-ethylhexyl) phthalate Macrophage Cytokines Chemokines DNA microarray analysis
This study was supported in part by the Mizutani Foundation for Glycoscience (K.I.) and by a Grant-in-Aid (S0991013) from the Foundation of Strategic Research Projects in Private Universities from Ministry of Education, Culture, Sports, Science, and Technology, Japan.
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