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Enhancement of interleukin-4 production in activated CD4+ T cells by diphthalate plasticizers via increased NF-AT binding activity.

Abstract：

BACKGROUND:Diethylhexyl phthalate (DEHP) and diisononyl phthalate (DINP), two commonly used plasticizers in flexible polyvinylchloride formulations, have potentially adverse effects on human health. However, the influence of these diphthalates on allergic responses remains unclear. In this study we examined the effects of DEHP and DINP on IL-4 production in CD4+ T cells and the level of IgE in sera, critical hallmarks associated with allergic diseases. METHODS:Mouse T cells were exposed to two diphthalates in vitro and in vivo. The levels of IL-4 and IgE were determined by ELISA, and the degree of NF-AT activation was determined by IL-4 gene promoter assay and electrophoretic mobility shift assay. RESULTS AND DISCUSSION:Both DEHP and DINP significantly enhanced IL-4 production in activated CD4+ T cells in a concentration-dependent manner. Treatment with DEHP or DINP in vivo resulted in a significant increase of IL-4 production in CD4+ T cells and of IgE levels in sera. Furthermore, DEHP and DINP enhanced the activation of IL-4 gene promoter in EL4 T cells and the enhancing effect mapped to a region in the IL-4 promoter containing binding sites for a transcription factor, NF-AT. The activation of T cells resulted in markedly enhanced binding activities to the NF-AT site, which significantly increased upon addition of DEHP or DINP, indicating that NF-AT was involved in the enhancing effect of DEHP and DINP on IL-4 production. These findings suggest that both DEHP and DINP enhance allergic responses by enhancement of IL-4 production in CD4+ T cells via stimulation of NF-AT-binding activity.

journal_name

Int Arch Allergy Immunol

journal_title

International archives of allergy and immunology

authors

Lee MH,Park J,Chung SW,Kang BY,Kim SH,Kim TS

doi

10.1159/000078768

keywords:

subject

Has Abstract

pub_date

2004-07-01 00:00:00

pages

213-22

issue

3

eissn

1018-2438

issn

1423-0097

pii

78768

journal_volume

134

pub_type

杂志文章

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