Effects of diisononyl phthalate on atopic dermatitis in vivo and immunologic responses in vitro

Koike, E; Yanagisawa, R; Sadakane, K; Inoue, K; Ichinose, T; Takano, H

HERO ID

673237

Reference Type

Journal Article

Year

2010

Language

English

PMID

20064775

HERO ID 673237
In Press No
Year 2010
Title Effects of diisononyl phthalate on atopic dermatitis in vivo and immunologic responses in vitro
Authors Koike, E; Yanagisawa, R; Sadakane, K; Inoue, K; Ichinose, T; Takano, H
Journal Environmental Health Perspectives
Volume 118
Issue 4
Page Numbers 472-478
Abstract BACKGROUND: Diisononyl phthalate (DINP), a principal plasticizer in many polyvinyl chloride products, has been shown to have an adjuvant effect on immunoglobulin (Ig) production in mice. However, the effects of DINP on allergic diseases have not been fully elucidated. OBJECTIVES: In the present study we investigated the effects of DINP on atopic dermatitis (AD)-like skin lesions induced by Dermatophagoides pteronyssinus (Dp) in atopic-prone NC/Nga mice. METHODS: Mice were injected intradermally with Dp on their ears and were exposed to DINP (0, 0.15, 1.5, 15, or 150 mg/kg/day) intraperitoneally. We evaluated clinical scores, ear thickening, histologic findings, protein expression of cytokines/chemokines in the ear, and serum levels of Ig and histamine. Furthermore, we investigated the effects of DINP on bone-marrow-derived dendritic cells (BMDCs) or splenocytes in vitro. After exposure to DINP (0-100 microM), cells were evaluated for phenotype and function. RESULTS: DINP aggravated AD-like skin lesions related to Dp. The aggravation was consistent with eosinophilic inflammation, mast cell degranulation, and thymic stromal lymphopoietin (TSLP) expression in the ear. DINP enhanced the expression of cell surface activation markers on BMDCs and their production of TARC/CCL17 (thymus- and activation-regulated chemokine) and MDC/CCL22 (macrophage-derived chemokine), as well as their capacity to stimulate Dp-specific T-cell proliferation. DINP also enhanced interleukin-4 production and Dp-stimulated proliferation of splenocytes. CONCLUSIONS: DINP can aggravate AD-like skin lesions related to Dp. The mechanisms of the aggravation might be mediated, at least partly, through the TSLP-related activation of dendritic cells and by direct or indirect activation of the immune cells.
Doi 10.1289/ehp.0901255
Pmid 20064775
Wosid WOS:000276454800018
Url https://ehp.niehs.nih.gov/doi/10.1289/ehp.0901255
Is Certified Translation No
Dupe Override No
Is Public Yes
Language Text English
Keyword antigen-presenting activity; atopic dermatitis; bone-marrow-derived dendritic cells; chemokines; diisononyl phthalate; eosinophils; mast cells; splenocytes
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