PMID- 12709020
OWN - NLM
STAT- MEDLINE
DCOM- 20030627
LR  - 20190513
IS  - 0019-2805 (Print)
IS  - 1365-2567 (Electronic)
IS  - 0019-2805 (Linking)
VI  - 109
IP  - 1
DP  - 2003 May
TI  - Enhanced interleukin-4 production in CD4+ T cells and elevated immunoglobulin E 
      levels in antigen-primed mice by bisphenol A and nonylphenol, endocrine 
      disruptors: involvement of nuclear factor-AT and Ca2+.
PG  - 76-86
AB  - Bisphenol A (BPA) and p-nonylphenol (NP) are representative endocrine disruptors 
      (EDs) that may have adverse effects on human health. The influence of these 
      compounds on allergic immune responses remains unclear. In this study, we have 
      examined the effects of BPA and NP on production of interleukin-4 (IL-4), a 
      pro-inflammatory cytokine closely associated with allergic immune responses. Both 
      BPA and NP significantly enhanced IL-4 production in keyhole limpet haemocyanin 
      (KLH)-primed CD4+ T cells in a concentration-dependent manner. Treatment with BPA 
      or NP in vivo resulted in significant increase of IL-4 production in CD4+ T cells 
      and of antigen-specific immunoglobulin E (IgE) levels in the sera of KLH-primed 
      mice. Furthermore, BPA and NP 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 (NF)-AT. Activation of T lymphocytes by phorbol 
      12-myristate 13-acetate/ionomycin resulted in markedly enhanced binding 
      activities to the NF-AT site, which significantly increased upon addition of BPA 
      or NP, as demonstrated by the electrophoretic mobility shift assay, indicating 
      that the transcription factor NF-AT was involved in the enhancing effect of BPA 
      and NP on IL-4 production. The enhancement of IL-4 production by BPA or NP was 
      significantly reduced by nitrendipine, a blocker of Ca2+ influx, and by FK506, a 
      calcineurin inhibitor. FK506 inhibited the NF-AT-DNA binding activity and IL-4 
      gene promoter activity enhanced by BPA or NP. These results represent the first 
      report describing possible enhancement of allergic response by EDs through 
      increasing IL-4 production in CD4+ T cells and antigen-specific IgE levels in the 
      sera via the stimulation of Ca2+/calcineurin-dependent NF-AT activation.
FAU - Lee, Mee H
AU  - Lee MH
AD  - Immunology Laboratory, College of Pharmacy, Chonnam National University, Kwangju, 
      Republic of Korea.
FAU - Chung, Su W
AU  - Chung SW
FAU - Kang, Bok Y
AU  - Kang BY
FAU - Park, Jin
AU  - Park J
FAU - Lee, Choon H
AU  - Lee CH
FAU - Hwang, Seung Y
AU  - Hwang SY
FAU - Kim, Tae S
AU  - Kim TS
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Immunology
JT  - Immunology
JID - 0374672
RN  - 0 (Benzhydryl Compounds)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Estrogens, Non-Steroidal)
RN  - 0 (NFATC Transcription Factors)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Phenols)
RN  - 0 (Transcription Factors)
RN  - 207137-56-2 (Interleukin-4)
RN  - 37341-29-0 (Immunoglobulin E)
RN  - 79F6A2ILP5 (nonylphenol)
RN  - MLT3645I99 (bisphenol A)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Benzhydryl Compounds
MH  - CD4-Positive T-Lymphocytes/*drug effects/immunology
MH  - Calcium/immunology
MH  - Cells, Cultured
MH  - DNA-Binding Proteins/immunology
MH  - Dose-Response Relationship, Immunologic
MH  - Estrogens, Non-Steroidal/*pharmacology
MH  - Female
MH  - Immunoglobulin E/blood
MH  - Interleukin-4/*biosynthesis/genetics
MH  - Lymph Nodes/immunology
MH  - Lymphocyte Activation/immunology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - NFATC Transcription Factors
MH  - *Nuclear Proteins
MH  - Phenols/*pharmacology
MH  - Promoter Regions, Genetic/immunology
MH  - Transcription Factors/immunology
PMC - PMC1782943
EDAT- 2003/04/24 05:00
MHDA- 2003/06/28 05:00
PMCR- 2004/05/01
CRDT- 2003/04/24 05:00
PHST- 2003/04/24 05:00 [pubmed]
PHST- 2003/06/28 05:00 [medline]
PHST- 2003/04/24 05:00 [entrez]
PHST- 2004/05/01 00:00 [pmc-release]
AID - 1631 [pii]
AID - 10.1046/j.1365-2567.2003.01631.x [doi]
PST - ppublish
SO  - Immunology. 2003 May;109(1):76-86. doi: 10.1046/j.1365-2567.2003.01631.x.