title: Diisononyl phthalate aggravates allergic dermatitis by activation of NF-kB.
abstract: Several epidemiological studies have suggested a possible link between exposure to Diisononyl phthalate (DINP) and the development of allergies. These findings remain controversial since there is insufficient scientific evidence to assess the ability of DINP to influence allergic immune responses. In addition, the mechanisms behind DINP-caused allergic diseases have not been fully elucidated. In this study, Balb/c mice were orally exposed to DINP for 3 weeks and were then sensitized with fluorescein isothiocyanate (FITC). We showed that oral exposure to DINP could aggravate allergic-dermatitis-like lesions, indicated by an increase in the number of mast cells, and in increased skin edema in FITC-induced contact hypersensitivity. This deterioration was concomitant with increased total serum immunoglobulin-E and Th2 cytokines. We determined the oxidative damage and the activation of nuclear factor-kb (NF-kB). The data demonstrated that DINP could promote oxidative damage and the activation of NF-kB in the skin. The expression of thymic stromal lymphopoietin and the activation of signal transducer and activator of transcriptions 3, 5 and 6 were enhanced concomitant with exacerbated allergic dermatitis effects and the activation of NF-kB induced by DINP. These effects were alleviated by pyrollidine dithiocarbamate, an inhibitor of NF-kB. The results suggest that oral exposure to DINP aggravated allergic contact dermatitis, which was positively regulated via NF-kB.
authors.affiliation: Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan 430079, Hubei, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Kang
authors.affiliation: Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan 430079, Hubei, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Song
authors.affiliation: Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan 430079, Hubei, China.
authors.forename: Shiping
authors.initials: S
authors.lastname: Shen
authors.affiliation: Key Laboratory of the Three Gorges Reservoir Region's Eco-Environment, Ministry of Education, Chongqing University, Chongqing 400045, China.
authors.forename: Baizhan
authors.initials: B
authors.lastname: Li
authors.affiliation: Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan 430079, Hubei, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Yang
authors.affiliation: Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan 430079, Hubei, China.
authors.forename: Mingqing
authors.initials: M
authors.lastname: Chen
mesh_terms: D000284:Administration, Oral; D000818:Animals; D016207:Cytokines / Q000097:blood / Q000378:metabolism; D017449:Dermatitis, Allergic Contact / Q000209:etiology* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D016650:Fluorescein-5-isothiocyanate; D007073:Immunoglobulin E / Q000097:blood; D008297:Male; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D010795:Phthalic Acids / Q000008:administration & dosage / Q000633:toxicity*; D011759:Pyrrolidines / Q000494:pharmacology; D050791:STAT Transcription Factors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D012867:Skin / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D013859:Thiocarbamates / Q000494:pharmacology; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D016207:Cytokines; D016328:NF-kappa B; D010795:Phthalic Acids; D011759:Pyrrolidines; D050791:STAT Transcription Factors; D013859:Thiocarbamates; C020972:pyrrolidine dithiocarbamic acid; D007073:Immunoglobulin E; C012125:diisononyl phthalate; D016650:Fluorescein-5-isothiocyanate; D000094632:Thymic Stromal Lymphopoietin; C000721967:TSLP protein, mouse
keywords: NF-kB; allergic dermatitis; diisononyl phthalate (DINP); oxidative stress; thymic stromal lymphopoietin (TSLP)