Low and high levels of α-tocopherol exert opposite effects on IL-2 possibly through the modulation of PPAR-γ, IκBα, and apoptotic pathway in activated splenocytes

Chia Chien Hsieh, Ching Jang Huang, Bi Fong Lin

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)

Abstract

Objective: We previously demonstrated that a high dose of α-tocopheryl succinate inhibits interleukin-2 (IL-2) mRNA and production in autoimmune-prone MRL/lpr mice. In the present study, we investigated the regulation of α-tocopherol (αTOC) on IL-2 gene expression by examining the mRNA of IL-2, inhibitor κBα (IκBα), and peroxisome proliferator-activated receptor-γ (PPARγ). Methods: Messenger RNA expression in active splenocytes of BALB/c mice was investigated with reverse transcriptase polymerase chain reaction. Results: Levels of IL-2 mRNA in phorbol 12-myristate 13-acetate/ionomycin activated splenocytes and cytokine in T-helper-1 cells were increased by 50 μM of αTOC but decreased by 1 mM of αTOC. In addition, the IκBα gene expression significantly increased by the high dose (<500 μM) of αTOC, suggesting an inhibition on nuclear factor-κB pathway for activation of IL-2 expression. PPARγ mRNA level in activated splenocytes was upregulated by 1 mM of αTOC. PPARγ mRNA level in unstimulated splenocytes was upregulated by αTOC in a dose-dependent manner, suggesting that αTOC might enhance the PPARγ signaling pathway. High-dose αTOC induced apoptosis of splenocytes and inhibited phytohemagglutinin- stimulated T-cell proliferation. Conversely, the proliferative response of splenocytes was enhanced by 5 μM of αTOC. Low-dose (50 μM) αTOC increased IL-2 expression, which may have been due to the absence of downregulation of PPARγ and IκBα on the IL-2 gene. Conclusion: The results indicated that low and high doses of αTOC exert opposite effects on IL-2, possibly through modulation of PPARγ, IκBα, and apoptosis pathways. The present findings support our previous observation of opposite effects of low- and high-dose vitamin E on survival of MRL/lpr mice.

Original languageEnglish
Pages (from-to)433-440
Number of pages8
JournalNutrition
Volume22
Issue number4
DOIs
Publication statusPublished - 2006 Apr 1
Externally publishedYes

Keywords

  • α-Tocopherol
  • IκBα
  • Interleukin-2
  • Lymphocyte
  • Peroxisome proliferator-activated receptor-γ

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Nutrition and Dietetics

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