Exposure to 4-tert-octylphenol, an environmentally persistent alkylphenol, enhances interleukin-4 production in T cells via NF-AT activation

Mi H. Lee, Eugene Kim, Tae Sung Kim

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

4-tert-Octylphenol (OP) is a representative endocrine disruptor that may have adverse effects on human health. The influence of this compound on allergic immune responses remains unclear. In this study, we have examined the effects of OP on production of interleukin-4 (IL-4), a pro-inflammatory cytokine closely associated with allergic immune responses. OP significantly enhanced IL-4 production in antigen-primed T cells in a dose-dependent manner. Treatment with OP in vivo resulted in significant increase of IL-4 production in T cells and of IgE levels in sera of antigen-primed mice. Furthermore, OP enhanced the activation of IL-4 gene promoter in EL4 T cells transiently transfected with IL-4 promoter/reporter constructs, and the enhancing effect mapped to a region in the IL-4 promoter containing binding sites for nuclear factor of activated T cell (NF-AT). Activation of T cells by phorbol-12-myristate-13-acetate (PMA) resulted in markedly enhanced binding activities to the NF-AT site, which significantly increased upon addition of OP, indicating that the transcription factor NF-AT was involved in the enhancing effect of OP on IL-4 production. The enhancement of IL-4 production by OP was blocked by FK506, a calcineurin inhibitor, but not by the estrogen receptor (ER) antagonist ICI 182780. FK506 inhibited the NF-AT-DNA binding activity and IL-4 gene promoter activity enhanced by OP in a dose-dependent manner. These findings demonstrate that OP enhances IL-4 production in T cells via the stimulation of calcineurin-dependent NF-AT activation.

Original languageEnglish
Pages (from-to)19-28
Number of pages10
JournalToxicology and Applied Pharmacology
Volume197
Issue number1
DOIs
Publication statusPublished - 2004 May 15
Externally publishedYes

Fingerprint

NFATC Transcription Factors
T-cells
Interleukin-4
Chemical activation
T-Lymphocytes
Tacrolimus
Genes
4-tert-octylphenol
Endocrine Disruptors
Antigens
Calcineurin
Immunoglobulin E
Acetates
Transcription Factors
Binding Sites
Health
Cytokines

Keywords

  • alkylphenol
  • Allergy
  • AP
  • EDC
  • ELISA
  • endocrine-disrupting compound
  • enzyme-linked immunosorbent assay
  • ER
  • estrogen receptor
  • IL-4
  • interleukin-4
  • Interleukin-4
  • keyhole limpet hemocyanin
  • KLH
  • NF-AT
  • nuclear factor of activated T cell
  • Octylphenol
  • OP
  • T cell

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

Cite this

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title = "Exposure to 4-tert-octylphenol, an environmentally persistent alkylphenol, enhances interleukin-4 production in T cells via NF-AT activation",
abstract = "4-tert-Octylphenol (OP) is a representative endocrine disruptor that may have adverse effects on human health. The influence of this compound on allergic immune responses remains unclear. In this study, we have examined the effects of OP on production of interleukin-4 (IL-4), a pro-inflammatory cytokine closely associated with allergic immune responses. OP significantly enhanced IL-4 production in antigen-primed T cells in a dose-dependent manner. Treatment with OP in vivo resulted in significant increase of IL-4 production in T cells and of IgE levels in sera of antigen-primed mice. Furthermore, OP enhanced the activation of IL-4 gene promoter in EL4 T cells transiently transfected with IL-4 promoter/reporter constructs, and the enhancing effect mapped to a region in the IL-4 promoter containing binding sites for nuclear factor of activated T cell (NF-AT). Activation of T cells by phorbol-12-myristate-13-acetate (PMA) resulted in markedly enhanced binding activities to the NF-AT site, which significantly increased upon addition of OP, indicating that the transcription factor NF-AT was involved in the enhancing effect of OP on IL-4 production. The enhancement of IL-4 production by OP was blocked by FK506, a calcineurin inhibitor, but not by the estrogen receptor (ER) antagonist ICI 182780. FK506 inhibited the NF-AT-DNA binding activity and IL-4 gene promoter activity enhanced by OP in a dose-dependent manner. These findings demonstrate that OP enhances IL-4 production in T cells via the stimulation of calcineurin-dependent NF-AT activation.",
keywords = "alkylphenol, Allergy, AP, EDC, ELISA, endocrine-disrupting compound, enzyme-linked immunosorbent assay, ER, estrogen receptor, IL-4, interleukin-4, Interleukin-4, keyhole limpet hemocyanin, KLH, NF-AT, nuclear factor of activated T cell, Octylphenol, OP, T cell",
author = "Lee, {Mi H.} and Eugene Kim and Kim, {Tae Sung}",
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TY - JOUR

T1 - Exposure to 4-tert-octylphenol, an environmentally persistent alkylphenol, enhances interleukin-4 production in T cells via NF-AT activation

AU - Lee, Mi H.

AU - Kim, Eugene

AU - Kim, Tae Sung

PY - 2004/5/15

Y1 - 2004/5/15

N2 - 4-tert-Octylphenol (OP) is a representative endocrine disruptor that may have adverse effects on human health. The influence of this compound on allergic immune responses remains unclear. In this study, we have examined the effects of OP on production of interleukin-4 (IL-4), a pro-inflammatory cytokine closely associated with allergic immune responses. OP significantly enhanced IL-4 production in antigen-primed T cells in a dose-dependent manner. Treatment with OP in vivo resulted in significant increase of IL-4 production in T cells and of IgE levels in sera of antigen-primed mice. Furthermore, OP enhanced the activation of IL-4 gene promoter in EL4 T cells transiently transfected with IL-4 promoter/reporter constructs, and the enhancing effect mapped to a region in the IL-4 promoter containing binding sites for nuclear factor of activated T cell (NF-AT). Activation of T cells by phorbol-12-myristate-13-acetate (PMA) resulted in markedly enhanced binding activities to the NF-AT site, which significantly increased upon addition of OP, indicating that the transcription factor NF-AT was involved in the enhancing effect of OP on IL-4 production. The enhancement of IL-4 production by OP was blocked by FK506, a calcineurin inhibitor, but not by the estrogen receptor (ER) antagonist ICI 182780. FK506 inhibited the NF-AT-DNA binding activity and IL-4 gene promoter activity enhanced by OP in a dose-dependent manner. These findings demonstrate that OP enhances IL-4 production in T cells via the stimulation of calcineurin-dependent NF-AT activation.

AB - 4-tert-Octylphenol (OP) is a representative endocrine disruptor that may have adverse effects on human health. The influence of this compound on allergic immune responses remains unclear. In this study, we have examined the effects of OP on production of interleukin-4 (IL-4), a pro-inflammatory cytokine closely associated with allergic immune responses. OP significantly enhanced IL-4 production in antigen-primed T cells in a dose-dependent manner. Treatment with OP in vivo resulted in significant increase of IL-4 production in T cells and of IgE levels in sera of antigen-primed mice. Furthermore, OP enhanced the activation of IL-4 gene promoter in EL4 T cells transiently transfected with IL-4 promoter/reporter constructs, and the enhancing effect mapped to a region in the IL-4 promoter containing binding sites for nuclear factor of activated T cell (NF-AT). Activation of T cells by phorbol-12-myristate-13-acetate (PMA) resulted in markedly enhanced binding activities to the NF-AT site, which significantly increased upon addition of OP, indicating that the transcription factor NF-AT was involved in the enhancing effect of OP on IL-4 production. The enhancement of IL-4 production by OP was blocked by FK506, a calcineurin inhibitor, but not by the estrogen receptor (ER) antagonist ICI 182780. FK506 inhibited the NF-AT-DNA binding activity and IL-4 gene promoter activity enhanced by OP in a dose-dependent manner. These findings demonstrate that OP enhances IL-4 production in T cells via the stimulation of calcineurin-dependent NF-AT activation.

KW - alkylphenol

KW - Allergy

KW - AP

KW - EDC

KW - ELISA

KW - endocrine-disrupting compound

KW - enzyme-linked immunosorbent assay

KW - ER

KW - estrogen receptor

KW - IL-4

KW - interleukin-4

KW - Interleukin-4

KW - keyhole limpet hemocyanin

KW - KLH

KW - NF-AT

KW - nuclear factor of activated T cell

KW - Octylphenol

KW - OP

KW - T cell

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U2 - 10.1016/j.taap.2004.02.003

DO - 10.1016/j.taap.2004.02.003

M3 - Article

VL - 197

SP - 19

EP - 28

JO - Toxicology and Applied Pharmacology

JF - Toxicology and Applied Pharmacology

SN - 0041-008X

IS - 1

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