Keywords: 
• DEHP /
• inflammation /
• immunity /
• allergy /
• asthma /
• ERK/MAPK /
• IL^-1β /
• MMP-8

Abstract: To investigate the cellular immunotoxicity of DEHP and its possible mechanism, RT-PCR and ELISA method were used to explore effect of DEHP on mRNA and protein expression of IL^-1β and MMP-8 in THP-1 cells within the concentration range of 0.05 to 1 μmol·L^-1. Western Blot method was applied to examine the effect of DEHP on the phosphorylation level of ERK1/2. The effect of 1-50 μmol·L^-1 DEHP on the production of reactive oxygen species (ROS) was evaluated using 2', 7'-dichlorofluorescin diacetate (DCFH-DA) as a fluorescent probe. Results showed that DEHP (0.05 and 0.2 μmol·L^-1) significantly induced mRNA expression of IL^-1β and MMP-8 within 6 h (P < 0.05 or 0.01). DEHP (0.05-1 μmol·L^-1) could induce the protein expression of IL^-1β within 48 h stimulation, which displayed obvious dose-effect relationship with correlation coefficient of 0.937. MMP-8 protein expression was significantly enhanced by stimulation of 0.05 μmol·L^-1 DEHP for 6 h or 12 h (P < 0.05). 0.2 μmol·L^-1 DEHP rapidly induced the phosphorylation of ERK1/2 within 15-30 min. 1-50 μmol·L^-1 DEHP dose-dependently stimulated the production of cellular ROS. ERK/MAPK inhibitor (PD98059) significantly suppressed DEHP-induced MMP-8 secretion, while it did not show inhibitory effect on IL^-1β secretion. It was indicated that DEHP might induce the gene and protein expression of MMP-8 through ERK/MAPK signaling pathway, and induce the production of cellular ROS and the gene and protein expression of IL^-1β through other pathways. The function of immune system was accordingly impaired and inflammatory disorders such as asthma were induced. This study could provide a reference for the risk assessment of DEHP exposure.