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


OBJECTIVE
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.
Koike
Eiko
E
Environmental Health Sciences Division, National Institute for Environmental Studies, Tsukuba, Japan. ekoike@nies.go.jp
Yanagisawa
Rie
R
Sadakane
Kaori
K
Inoue
Ken-ichiro
K
Ichinose
Takamichi
T
Takano
Hirohisa
H
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects; D003876:Dermatitis, Atopic / Q000097:blood / Q000139:chemically induced* / Q000276:immunology* / Q000469:parasitology; D040002:Dermatophagoides pteronyssinus / Q000472:pathogenicity; D005434:Flow Cytometry; D006632:Histamine / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D051379:Mice; D010795:Phthalic Acids / Q000009:adverse effects*
D007074:Immunoglobulin G; D010795:Phthalic Acids; C012125:diisononyl phthalate; D006632:Histamine