Suppression of Sirtuin-1 Increases IL-6 Expression by Activation of the Akt Pathway During Allergic Asthma
Suppression of Sirtuin-1 Increases IL-6 Expression by Activation of the Akt Pathway During Allergic Asthma
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过敏性哮喘期间抑制 Sirtuin-1 通过激活 Akt 通路增加 IL-6 表达
DOI：
10.1159/000484119
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发表时间：
2017-10
期刊：
影响因子：
--
通讯作者：
Wang Xiongbiao
中科院分区：
文献类型：
--
作者：
Tang Lingling;Chen Qingge;Meng Ziyu;Sun Li;Zhu Linyun;Liu Jinjin;Hu Junsheng;Ni Zhenhua;Wang Xiongbiao
背景/目标：越来越多的研究表明，哮喘患者SIRT 1的活性和表达水平降低，但SIRT 1表达和功能降低的机制尚不完全清楚。白细胞介素-6（IL-6）在过敏性哮喘的炎症反应中起重要作用。在这项研究中，我们研究了SIRT 1活性的丧失是否调节IL-6的表达，并进一步验证了潜在的机制。方法：采用人气道上皮细胞系16 HBE，观察SIRT 1抑制剂沙勒米特对IL-6表达的影响。采用实时荧光定量PCR、免疫组化和ELISA检测IL-6 mRNA和蛋白表达。以OVA激发的小鼠作为哮喘模型，研究SIRT 1激活对IL-6和相对Akt磷酸化水平的影响。结果如下：我们发现SIRT 1的抑制以时间依赖性的方式增加IL-6 mRNA和蛋白水平，这伴随着16 HBE细胞中Akt通路激活的增加。此外，Akt的活化显示IL-6蛋白的表达上调，而Akt抑制剂LY 294002或Akt siRNA显著抑制SIRT 1调节的IL-6表达。相反，SIRT 1的激活抑制哮喘小鼠模型和16 HBE细胞中Akt的激活和IL-6的表达。结论：我们的研究结果表明，SIRT 1在调节炎症的潜在作用，通过调节IL-6的表达在Akt依赖性的方式在过敏性哮喘。
Background/Aims: A growing number of studies have demonstrated that the activity and expression level of sirtuin-1 (SIRT1) are decreased in asthma patients; however, the mechanisms underlying decreased SIRT1 expression and function are still not completely understood. Interleukin (IL)-6 plays important roles in inflammation during allergic asthma. In this study, we examined whether loss of SIRT1 activity regulated the expression of IL-6 and further verified the underlying mechanisms. Methods: The human airway epithelial cell line 16HBE was used to test the effects of the SIRT1 inhibitor (salermide) on expression of IL-6. IL-6 mRNA and protein expression were assessed with real-time polymerase chain reaction (PCR), immunochemistry, and ELISA. OVA-challenged mice were used as an asthma model to investigate the effect of SIRT1 activation on IL-6 and relative Akt phosphorylation level. Results: We found that inhibition of SIRT1 increased IL-6 mRNA and protein levels in a time-dependent manner, which was accompanied by increased Akt pathway activation in 16HBE cells. Furthermore activation of Akt showed upregulated expression of the IL-6 protein whereas Akt inhibitor, LY294002 or Akt siRNA significantly inhibited SIRT1-regulated IL-6 expression. Conversely, activation of SIRT1 inhibited Akt activation and IL-6 expression in an asthmatic mice model and 16HBE cells. Conclusion: Our results indicate the potential role of SIRT1 in regulating inflammation by modulation of IL-6 expression in an Akt-dependent manner during allergic asthma.
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白藜芦醇抑制哮喘小鼠模型中粘液过量产生和 MUC5AC 表达
影响因子：
3.4
作者：
Ni, Zhen-Hua;Tang, Ji-Hong;Wang, Xiong-Biao
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DOI：
10.1152/ajpendo.00417.2009
发表时间：
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影响因子：
5.1
作者：
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通讯作者：
Olefsky, Jerrold M.
影响因子：
3
作者：
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影响因子：
5.5
作者：
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M. Bracke;E. A. van de Graaf;J. Lammers;P. Coffer;L. Koenderman
影响因子：
--
作者：
Lin, Zhenghong;Fang, Deyu
通讯作者：
Fang, Deyu