Down-regulation of T-cell interleukin-2 production by dietary N-3 fatty acids is independent of interleukin-2 gene transcription
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We have previously shown that highly purified dietary eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) suppress T-cell interleukin-2 (IL-2) protein production and subsequent proliferation. To determine if the mechanism of suppression of IL-2 production is pre- or post-transcriptional in nature, mice (n=10) were fed diets for 10 days containing either: 3% (wt/wt) safflower oil ethyl esters containing primarily linoleic acid [SAF] (control), 2% SAF + 1% EPA ethyl esters, 2% SAF + 1% DHA ethyl esters, or 2% SAF +1% arachidonic acid [AA] as triglyceride. Splenic lymphocytes were isolated and either analyzed for T-cell subsets (CD4+ and CD8+) by flow cytometry or activated in vitro with concanavalin A (con A), a polyclonal T-cell mitogen. Steady-state mRNA levels for IL-2 and IL-2 receptor -chain at 0, 3, 6, and 9 h were determined by relative competitive-polymerase chain reaction. Dietary EPA and DHA did not significantiy affect the overall proportion of CD4+ and CD8+ T-cells compared to SAF and AA fed animals. Furthermore, maximal production of IL-2 mRNA was not affected by EPA or DHA feeding. In contrast, DHA fed mice showed a significant (p<0.05) increase (75%) in IL-2 receptor mRNA levels at 9 h post-mitogen addition relative to EPA, SAF and AA fed mice. These data suggest that the reduced levels of released IL-2 are the result of post-transcriptional events, and that the impaired proliferative responses in T-cells from EPA and DHA fed mice do not result from down-regulation of IL-2 receptor message.