Truncated deoxynivalenol-induced splenic immediate early gene response in mice consuming (n-3) polyunsaturated fatty acids.
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.
Kinser
Shawn
S
Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI 48824-1224, USA.
Li
Maioxing
M
Jia
Qunshan
Q
Pestka
James J
JJ
D000818:Animals; D018925:Chemokines / Q000235:genetics; D003314:Corn Oil / Q000008:administration & dosage; D016207:Cytokines / Q000235:genetics; D004042:Dietary Fats, Unsaturated / Q000008:administration & dosage*; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage*; D015870:Gene Expression / Q000187:drug effects*; D017781:Genes, Immediate-Early / Q000235:genetics*; D007700:Kinetics; D008297:Male; D051379:Mice; D019301:Oleic Acid / Q000008:administration & dosage; D016133:Polymerase Chain Reaction; D013154:Spleen / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000235:genetics; D014255:Trichothecenes / Q000494:pharmacology*
D018925:Chemokines; D016207:Cytokines; D004042:Dietary Fats, Unsaturated; D015525:Fatty Acids, Omega-3; D018808:Transcription Factor AP-1; D014255:Trichothecenes; D019301:Oleic Acid; D003314:Corn Oil; C007262:deoxynivalenol