title: Diisononyl phthalate induces asthma via modulation of Th1/Th2 equilibrium.
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.
authors.affiliation: College of Pharmacy, Sunchon National University, 255 Jungangno, Suncheon 540-950, Republic of Korea.
authors.forename: Yun-Ho
authors.initials: YH
authors.lastname: Hwang
authors.affiliation: College of Pharmacy, Sunchon National University, 255 Jungangno, Suncheon 540-950, Republic of Korea.
authors.forename: Man-Jeong
authors.initials: MJ
authors.lastname: Paik
authors.affiliation: College of Pharmacy, Sunchon National University, 255 Jungangno, Suncheon 540-950, Republic of Korea; Suncheon Research Center for Natural Medicines, Suncheon, Republic of Korea. Electronic address: sungtae@sunchon.ac.kr.
authors.forename: Sung-Tae
authors.initials: ST
authors.lastname: Yee
mesh_terms: D000818:Animals; D001249:Asthma / Q000139:chemically induced* / Q000276:immunology; D016764:Cell Polarity / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D004785:Environmental Pollutants / Q000633:toxicity*; D007136:Immunoglobulins / Q000276:immunology / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology; D010795:Phthalic Acids / Q000633:toxicity*; D018417:Th1 Cells / Q000187:drug effects* / Q000276:immunology; D058408:Th1-Th2 Balance / Q000187:drug effects; D018418:Th2 Cells / Q000187:drug effects* / Q000276:immunology
chemical_list: D016207:Cytokines; D004785:Environmental Pollutants; D007136:Immunoglobulins; D010795:Phthalic Acids; C012125:diisononyl phthalate; D010047:Ovalbumin
keywords: Airway hyperresonsiveness (AHR); Asthma; Diisononyl phthalate (DINP); Endocrine disruptor (ECD); Environmental pollutant; Helper T cells (Th cells)