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抑制NHE1可下调白细胞介素-8的表达并增强p38磷酸化

[Inhibition of NHE1 down-regulates IL-8 expression and enhances p38 phosphorylation].

作者信息

Gao Wei, Zhang Yu-Juan, Zhang Hai-Rui, Jin Wei-Na, Chang Guo-Qiang, Zhang Hong-Ju, Ma Li, Lin Ya-Ni, Li Qing-Hua, Ru Rong-Xin, Pang Tian-Xiang

机构信息

Chinese Academy of Medical Sciences, Tianjin, China.

出版信息

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2013 Feb;21(1):45-8. doi: 10.7534/j.issn.1009-2137.2013.01.010.

Abstract

This study was purposed to explore the changes of possible angiogenetic factors other than VEGF after inhibition of NHE1 and their related mechanisms. The K562 cells were treated by NHE1 specific inhibitor cariporide, the angiogenesis factors after inhibition of NHE1 were screened by using protein chip, the IL-8 expression level after cariporide treatment was detected by real-time quantitative PCR; the K562 cells with stable interference of NHE1 were constructed, the IL-8 expression level after interference of NHE1 was detected by real-time quantitative PCR; the p38 phosphorylation level in K562 cells treated with cariporide was detected by Western blot. After treatment of K562 cells with p38 inhibitor SB203580, the IL-8 expression level was decreased by real-time quantitative PCR. The results of protein chip showed that IL-8 expression decreased after cariporide treatment. Real-time quantitative PCR confirmed this inhibitory effect. The p38 phosphorylation level increased after cariporide treatment. The down-regulation of IL-8 expression induced by cariporide treatment was partially restored after K562 cells were treated with p38 inhibitor SB203580. It is concluded that the inhibition of NHE1 can inhibit IL-8 expression through up-regulation of p38 phosphorylation.

摘要

本研究旨在探讨抑制NHE1后除VEGF外其他可能的血管生成因子的变化及其相关机制。用NHE1特异性抑制剂卡立泊来处理K562细胞,采用蛋白质芯片筛选抑制NHE1后的血管生成因子,用实时定量PCR检测卡立泊来处理后IL-8的表达水平;构建稳定干扰NHE1的K562细胞,用实时定量PCR检测干扰NHE1后IL-8的表达水平;用蛋白质印迹法检测卡立泊来处理的K562细胞中p38磷酸化水平。用p38抑制剂SB- ​​203580处理K562细胞后,通过实时定量PCR检测IL-8表达水平降低。蛋白质芯片结果显示,卡立泊来处理后IL-8表达降低。实时定量PCR证实了这种抑制作用。卡立泊来处理后p38磷酸化水平升高。用p38抑制剂SB- ​​203580处理K562细胞后,卡立泊来处理诱导的IL-8表达下调部分恢复。结论是,抑制NHE1可通过上调p38磷酸化来抑制IL-8表达。

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