Diisononyl phthalate induces asthma via modulation of Th1/Th2 equilibrium. (15th April 2017)

• Record Type: Journal Article
• Authors: Hwang, Yun-Ho; Paik, Man-Jeong; Yee, Sung-Tae
• Is Part Of: Toxicology letters. Volume 272(2017)
• Page Start: 49
• Page End: 59
• Publication Date: 2017-04-15
• Subjects: Asthma -- Airway hyperresonsiveness (AHR) -- Helper T cells (Th cells) -- Diisononyl phthalate (DINP) -- Endocrine disruptor (ECD) -- Environmental pollutant; Toxicology -- Periodicals; 363.179
• DOI: 10.1016/j.toxlet.2017.03.014
• Languages: English
• ISSNs: 0378-4274

Abstract

Graphical abstract: Highlights: DINP suppresses Th1 polarization and enhances Th2 polarization in vitro. DINP induces airway hyperresonsiveness in vivo. DINP induces Th2 mediated cytokine (IL-4, IL-5) and immunoglobulin (IgE, IgG1). DINP induces airway inflammation and enhancement of the goblet cells in lung. DINP induces expression of caspase-1 and caspase-3 in lung. Abstract: Diisononyl phthalate (DINP), a member of the phthalate family, is used to plasticize polyvinyl chloride (PVC). This chemical is known to enhance airway inflammation in the OVA-induced asthma model (adjuvant effects) and aggravate allergic dermatitis. Moreover, DINP enhances the production of interleukin-4 in activated CD4 + T cells. However, the effect of DINP itself on the differentiation of naïve CD4 + T cells into T helper cells (Th1/Th2) in vitro and allergic asthma in vivo has not yet been studied. In this study, DINP was shown to suppress the polarization of Th1 and enhance the polarization of Th2 from naïve CD4 + T cells in vitro. Also, DINP induced allergic asthma via the production of IL-4, IL-5, IgE and IgG1 and the reduction of IFN-γ and IgG2a. Finally, we confirmed that exposure to DINP induces the infiltration of inflammatory cells and PAS positive cells and increases the expression of caspase-1 and caspase-3 in asthmatic mice. In conclusion, we suggest that DINP as an environmental pollutant or endocrine disruptor (ECD) induces asthma via the modulation of the Th1/Th2 equilibrium and production of Th2 mediated cytokines and immunoglobulin.