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十四烷醇通过下调核因子κB介导的白细胞介素-2分泌来抑制EL-4 T细胞生长。

Tetradecanol reduces EL-4 T cell growth by the down regulation of NF-κB mediated IL-2 secretion.

作者信息

Park Jung Up, Kang Bok Yun, Lee Hwa-Jeong, Kim Sunoh, Bae Donghyuck, Park Jong-Hwan, Kim Young Ran

机构信息

College of Pharmacy and Research Institute of Drug Development, Chonnam National University, Gwangju 500-757, Republic of Korea.

Department of Biomedical Science, Chonnam National University Medical School, Gwangju 500-757, Republic of Korea.

出版信息

Eur J Pharmacol. 2017 Mar 15;799:135-142. doi: 10.1016/j.ejphar.2017.02.002. Epub 2017 Feb 3.

Abstract

Tetradecanol is a straight-chain saturated fatty alcohol purified from Dendropanax morbifera leaves. We found that tetradecanol (30μM) reduced specifically the growth of T cells such as EL-4 T cell and isolated murine CD4 T cells. In this study, we investigated the effects of tetradecanol on the regulation of interlukin-2 (IL-2), a potent T cell growth factor. Tetradecanol significantly inhibited IL-2 secretion in EL-4 T cells activated with phorbol 12-myristate 13-acetate (PMA) plus ionomycin (Io) and also in isolated murine CD4 T cells activated with anti-CD3 and anti-CD28 antibodies. Next, we examined the effect of tetradecanol on the transcriptional activity related to IL-2 production in T cells. Tetradecanol decreased PMA/Io-induced promoter activity of NF-κB in EL-4 T cells, but did not show any significant effects on the promoters of activator protein 1 (AP-1) and nuclear factor of activated T cells (NF-AT). Tetradecanol inhibited IκBα degradation and nuclear translocation of NF-κB subunit, p65 in PMA/Io-activated EL-4 T cells. These results suggest that tetradecanol might have immunosuppressive effects on T cell mediated disorders. Using a chronic allergic contact dermatitis model induced by repeated application of oxazolone, we showed that tetradecanol reduced ear thickness induced by oxazolone.

摘要

十四烷醇是一种从辽东楤木叶中提纯的直链饱和脂肪醇。我们发现,十四烷醇(30μM)能特异性地抑制诸如EL-4 T细胞和分离出的小鼠CD4 T细胞等T细胞的生长。在本研究中,我们探究了十四烷醇对强效T细胞生长因子白细胞介素-2(IL-2)调节的影响。十四烷醇显著抑制了用佛波酯12-肉豆蔻酸酯13-乙酸酯(PMA)加离子霉素(Io)激活的EL-4 T细胞以及用抗CD3和抗CD28抗体激活的分离小鼠CD4 T细胞中IL-2的分泌。接下来,我们检测了十四烷醇对T细胞中与IL-2产生相关的转录活性的影响。十四烷醇降低了PMA/Io诱导的EL-4 T细胞中NF-κB的启动子活性,但对活化蛋白1(AP-1)和活化T细胞核因子(NF-AT)的启动子没有显著影响。十四烷醇抑制了PMA/Io激活的EL-4 T细胞中IκBα的降解以及NF-κB亚基p65的核转位。这些结果表明,十四烷醇可能对T细胞介导的疾病具有免疫抑制作用。通过使用反复涂抹恶唑酮诱导的慢性过敏性接触性皮炎模型,我们发现十四烷醇降低了恶唑酮诱导的耳部厚度。

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