Exposure to diisodecyl phthalate exacerbated Th2 and Th17-mediated asthma through aggravating oxidative stress and the activation of p38 MAPK.

Diisodecyl phthalate (DIDP) is considered to be one of the less toxic phthalates. However epidemiological studies suggest that DIDP is associated with the occurrence of asthma. The effect of DIDP exposure on allergic asthma and the underlying mechanism have not been fully elucidated. Here, mice were exposed to DIDP and sensitization with OVA. The results demonstrated that DIDP exposure aggravated allergic asthma. Exposure to 15 mg/kg/day DIDP markedly exacerbated airway remodeling and promoted airway hyperresponsiveness (AhR). The study suggests that exposure to DIDP not only promotes a predominant Th2 response, but also induces Th17-type immunity. The induced allergic asthma was accompanied by elevation of IgE, an increase in TSLP expression and exacerbation of oxidative stress. Inhibition of oxidative stress by Vitamin E effectively alleviated the airway remodeling and AhR induced by DIDP and OVA sensitization. Treatment with Vitamin E inhibited the Th2 response and the production of TSLP. Blocking the activation of p38 MAPK by SB203580 prevented elevation of IL-1β and IL-17A induced by DIDP and OVA sensitization and effectively alleviated Th17 type asthmatic lesions. These results suggest that exposure to DIDP exacerbates the Th2 and Th17 response through aggravating oxidative stress and activation of the p38 MAPK pathway.