Document Detail

Truncated deoxynivalenol-induced splenic immediate early gene response in mice consuming (n-3) polyunsaturated fatty acids.
MedLine Citation:
PMID:  15681167     Owner:  NLM     Status:  MEDLINE    
Expression profiling has previously revealed that acute exposure to the common foodborne mycotoxin deoxynivalenol (DON) induces a large number of immediate early genes in murine lymphoid tissues that potentially affect immune function. The purpose of this study was to test the hypothesis that consumption of (n-3) polyunsaturated fatty acids (PUFAs) found in fish oil interferes with DON-induced immediate early gene expression. Mice were fed AIN-93G diet containing 1% corn oil (CO) plus 6% oleic acid (control) or a diet containing 1% CO, 2% fish oil enriched in the (n-3)-PUFAs docosahexaenoic and eicosapentaenoic acid and 4% oleic acid. After 12 weeks, the mice were gavaged orally with 25 mg/kg DON and the kinetics of immediate early gene expression in spleen monitored over 8 h by real-time polymerase chain reaction (PCR). Deoxynivalenol was found to readily induce expression of cytokines (IL-1alpha, IL-1beta, and IL-6 and IL-11), chemokines (MCP-1, MCP-3, CINC-1 and MIP-2), components of the activator protein-1 (AP-1) transcription factor complex (c-Fos, Fra-2, c-Jun and JunB), as well as two hydrolases (MKP1, CnAbeta). Expression of these genes was transient, peaking within 2-4 h and declining thereafter, with the single exception being IL-11 that was elevated at 8 h. (n-3)-PUFA consumption significantly suppressed DON-induced expression of IL-1alpha, IL-6, IL-11, MCP-1, MCP-3, MIP-2 and Fra-2 at 8 h. In contrast, mice fed (n-3)-PUFA exhibited significant increases in MKP1 and CnAbeta expression. Taken together, these data suggest that dietary supplementation with (n-3)-PUFAs prematurely truncated cytokine, chemokine and transcription factor expression responses to DON that may impact its previously described capacity to disrupt immune function including immunoglobulin A (IgA) production. Since expression of many of these genes has been linked to mitogen-activated protein kinase (MAPK) activation, enhanced expression of MKP1, a negative MAPK regulator in (n-3)-PUFA-fed mice might contribute to this suppression.
Shawn Kinser; Maioxing Li; Qunshan Jia; James J Pestka
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of nutritional biochemistry     Volume:  16     ISSN:  0955-2863     ISO Abbreviation:  J. Nutr. Biochem.     Publication Date:  2005 Feb 
Date Detail:
Created Date:  2005-01-31     Completed Date:  2005-07-05     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  9010081     Medline TA:  J Nutr Biochem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  88-95     Citation Subset:  IM    
Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI 48824-1224, USA.
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MeSH Terms
Chemokines / genetics
Corn Oil / administration & dosage
Cytokines / genetics
Dietary Fats, Unsaturated / administration & dosage*
Fatty Acids, Omega-3 / administration & dosage*
Gene Expression / drug effects*
Genes, Immediate-Early / genetics*
Oleic Acid / administration & dosage
Polymerase Chain Reaction
Spleen / metabolism*
Transcription Factor AP-1 / genetics
Trichothecenes / pharmacology*
Grant Support
Reg. No./Substance:
0/Chemokines; 0/Cytokines; 0/Dietary Fats, Unsaturated; 0/Fatty Acids, Omega-3; 0/Transcription Factor AP-1; 0/Trichothecenes; 112-80-1/Oleic Acid; 51481-10-8/deoxynivalenol; 8001-30-7/Corn Oil

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