Di-(2-ethylhexyl) phthalate induces production of inflammatory molecules in human macrophages.

ABSTRACT

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-1ß, 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. RESULTS: DEHP treatment increased the concentrations of TNF-α, IL-1ß, 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-1ß, and IL-6 mRNA in THP-1 cells. DEHP significantly induced translocation of p65 NF-κB into the nucleus. CONCLUSION: DEHP enhances the production of inflammatory cytokines and chemokines by macrophages, and exacerbates their inflammatory response.