抑制钠氢交换蛋白下调IL-8表达和促进p38磷酸化  

Inhibition of NHE1 Down-regulates IL-8 Expression and Enhances p38 Phosphorylation

作　　者：高伟[1,2] 张玉娟[1] 张海瑞[1] 金薇娜[1] 常国强[1] 张洪菊[1] 马丽[1] 蔺亚妮[1] 李庆华[1] 茹永新[1] 庞天翔[1] 

机构地区：[1]中国医学科学院,北京协和医学院血液学研究所,血液病医院,实验血液学国家重点实验室,天津300020 [2]潍坊医学院病理生理学教研室,山东潍坊261053

出　　处：《中国实验血液学杂志》2013年第1期45-48,共4页Journal of Experimental Hematology

基　　金：国家自然科学基金(编号81170510);高等学校博士学科点专项科研基金(编号20091106110038)

摘　　要：我们前期的研究证明,抑制钠氢交换蛋白1(NHE1)可以减少VEGF表达从而抑制K562细胞诱导的血管生成。本研究探讨抑制NHE1后其他可能的血管生成因子变化及相关机制。用NHE1特异性抑制剂卡立泊来德10μmol/L处理K562细胞;蛋白芯片筛选NHE1抑制后血管生成因子的表达变化,实时定量PCR验证卡立泊来德处理后白介素-8(IL-8)的表达水平;构建K562稳定干扰NHE1细胞株,实时定量PCR验证干扰NHE1后IL-8的表达变化,Western blot检测卡立泊来德处理后细胞内p38磷酸化水平;p38抑制剂SB203580处理K562细胞,实时定量检测IL-8表达变化。蛋白芯片筛选结果显示,卡立泊来德处理后K562细胞中IL-8表达显著下调;实时定量结果进一步验证了这种抑制效应;卡立泊来德处理后p38磷酸化水平显著上调;卡立泊来德处理后加入SB203580抑制p38,IL-8表达可以部分恢复。结论:抑制NHE1可能通过促进p38磷酸化,下调促血管生成因子IL-8的表达。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 factots after inhibition of NHEl 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 contructed, the IL-8 expression level after interference of NHE1 was detected by real-time quantitative PCR; the p38 phosphorylation level in K562 cels treated with caripodde 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.

关 键 词：钠氢交换蛋白1 卡立泊来德 K562细胞 血管生成因子 白介素-8 p38 白血病 

分 类 号：R733.7[医药卫生—肿瘤]