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Effects of diisononyl phthalate on atopic dermatitis in vivo and immunologic responses in vitro.
Environ Health Perspect. 2010 Apr; 118(4):472-8.EH

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.

Authors+Show Affiliations

Environmental Health Sciences Division, National Institute for Environmental Studies, Tsukuba, Japan. ekoike@nies.go.jpNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20064775

Citation

Koike, Eiko, et al. "Effects of Diisononyl Phthalate On Atopic Dermatitis in Vivo and Immunologic Responses in Vitro." Environmental Health Perspectives, vol. 118, no. 4, 2010, pp. 472-8.
Koike E, Yanagisawa R, Sadakane K, et al. Effects of diisononyl phthalate on atopic dermatitis in vivo and immunologic responses in vitro. Environ Health Perspect. 2010;118(4):472-8.
Koike, E., Yanagisawa, R., Sadakane, K., Inoue, K., Ichinose, T., & Takano, H. (2010). Effects of diisononyl phthalate on atopic dermatitis in vivo and immunologic responses in vitro. Environmental Health Perspectives, 118(4), 472-8. https://doi.org/10.1289/ehp.0901255
Koike E, et al. Effects of Diisononyl Phthalate On Atopic Dermatitis in Vivo and Immunologic Responses in Vitro. Environ Health Perspect. 2010;118(4):472-8. PubMed PMID: 20064775.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of diisononyl phthalate on atopic dermatitis in vivo and immunologic responses in vitro. AU - Koike,Eiko, AU - Yanagisawa,Rie, AU - Sadakane,Kaori, AU - Inoue,Ken-ichiro, AU - Ichinose,Takamichi, AU - Takano,Hirohisa, Y1 - 2009/11/19/ PY - 2009/07/27/received PY - 2009/11/19/accepted PY - 2010/1/13/entrez PY - 2010/1/13/pubmed PY - 2010/7/16/medline SP - 472 EP - 8 JF - Environmental health perspectives JO - Environ Health Perspect VL - 118 IS - 4 N2 - 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. SN - 1552-9924 UR - https://www.unboundmedicine.com/medline/citation/20064775/Effects_of_diisononyl_phthalate_on_atopic_dermatitis_in_vivo_and_immunologic_responses_in_vitro_ L2 - https://ehp.niehs.nih.gov/doi/10.1289/ehp.0901255?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -