https://scholars.lib.ntu.edu.tw/handle/123456789/138426
Title: | 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 | Authors: | Hsieh, Chia-Chien Huang, Ching-Jang Hsieh CC |
Keywords: | α-Tocopherol; IκBα; Interleukin-2; Lymphocyte; Peroxisome proliferator-activated receptor-γ | Issue Date: | 2006 | Journal Volume: | 22 | Journal Issue: | 4 | Start page/Pages: | 433-440 | Source: | Nutrition | 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. © 2006 Elsevier Inc. All rights reserved. |
URI: | http://ntur.lib.ntu.edu.tw//handle/246246/162588 http://ntur.lib.ntu.edu.tw/bitstream/246246/162588/1/21.pdf https://www.scopus.com/inward/record.uri?eid=2-s2.0-33644855510&doi=10.1016%2fj.nut.2005.10.001&partnerID=40&md5=a3b912932ccadd5c17c2be4f9b6a3b06 |
ISSN: | 08999007 | DOI: | 10.1016/j.nut.2005.10.001 | SDG/Keyword: | alpha tocopherol; cytokine; I kappa B; immunoglobulin enhancer binding protein; interleukin 2; ionomycin; messenger RNA; peroxisome proliferator activated receptor gamma; phorbol 13 acetate 12 myristate; phytohemagglutinin; animal cell; animal experiment; animal tissue; apoptosis; article; cell activation; cell stimulation; concentration response; controlled study; cytokine release; down regulation; drug inhibition; drug megadose; female; gene expression; lymphocyte proliferation; mouse; nonhuman; priority journal; receptor upregulation; reverse transcription polymerase chain reaction; spleen cell; T lymphocyte; Th1 cell; alpha-Tocopherol; Animals; Antioxidants; Apoptosis; Cells, Cultured; Dose-Response Relationship, Drug; Female; Gene Expression Regulation; I-kappa B Proteins; Interleukin-2; Mice; Mice, Inbred BALB C; PPAR gamma; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Spleen; Animalia |
Appears in Collections: | 生化科技學系 |
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