Document Detail


Th2 skewing by activation of Nrf2 in CD4(+) T cells.
MedLine Citation:
PMID:  22250088     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
NF erythroid 2-related factor 2 (Nrf2) is a transcription factor that mediates the upregulation of a battery of cytoprotective genes in response to cell stress. Recent studies showed that Nrf2 also modulates immune responses and exhibits anti-inflammatory activity. In this article, we demonstrate that a common food preservative, tert-butylhydroquinone, can activate Nrf2 in T cells, as evidenced by Nrf2 binding to the antioxidant response element and the subsequent upregulation of Nrf2 target genes. The activation of Nrf2 suppresses IFN-γ production, while inducing the production of the Th2 cytokines IL-4, IL-5, and IL-13. Nrf2 activation also suppresses T-bet DNA binding and promotes GATA-binding protein 3 DNA binding. Collectively, the present studies suggested that Nrf2 activation skews CD4(+) T cells toward Th2 differentiation and, thus, represents a novel regulatory mechanism in CD4(+) T cells. Further studies are needed to determine whether the commercial use of Nrf2 activators as food preservatives promotes food allergies in humans.
Authors:
Cheryl E Rockwell; Mingcai Zhang; Patrick E Fields; Curtis D Klaassen
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-01-16
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  188     ISSN:  1550-6606     ISO Abbreviation:  J. Immunol.     Publication Date:  2012 Feb 
Date Detail:
Created Date:  2012-02-06     Completed Date:  2012-03-26     Revised Date:  2013-12-12    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1630-7     Citation Subset:  AIM; IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
CD4-Positive T-Lymphocytes / immunology,  metabolism*
Cell Differentiation / drug effects
Cells, Cultured
Female
Food Hypersensitivity
Food Preservatives / pharmacology*
GATA3 Transcription Factor / metabolism
Hydroquinones / pharmacology*
Interferon-gamma / biosynthesis
Interleukin-13 / biosynthesis
Interleukin-4 / biosynthesis
Interleukin-5 / biosynthesis
Luciferases / metabolism
Mice
Mice, Inbred AKR
Mice, Inbred C57BL
NF-E2-Related Factor 2 / biosynthesis,  metabolism*
T-Box Domain Proteins / antagonists & inhibitors,  metabolism
Th2 Cells / immunology*,  metabolism
Grant Support
ID/Acronym/Agency:
K99 ES018885/ES/NIEHS NIH HHS; K99 ES018885/ES/NIEHS NIH HHS; K99 ES018885-02/ES/NIEHS NIH HHS; P20 RR016475/RR/NCRR NIH HHS; R01 DK081461/DK/NIDDK NIH HHS; T32 ES007079/ES/NIEHS NIH HHS
Chemical
Reg. No./Substance:
0/Food Preservatives; 0/GATA3 Transcription Factor; 0/Hydroquinones; 0/Interleukin-13; 0/Interleukin-5; 0/NF-E2-Related Factor 2; 0/Nfe2l2 protein, mouse; 0/T-Box Domain Proteins; 0/T-box transcription factor TBX21; 207137-56-2/Interleukin-4; 82115-62-6/Interferon-gamma; C12674942B/2-tert-butylhydroquinone; EC 1.13.12.-/Luciferases
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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