HHIP基因在吸烟介导的气道炎症中的作用

目的 以香烟提取物刺激HHIP基因沉默的A549细胞与正常对照组细胞,比较其释放炎症介质的mRNA和蛋白表达水平差异,从而探讨HHIP基因在吸烟介导的气道炎症反应中的调控作用.方法 将A549细胞分为对照组与实验组,以siRNA技术瞬时沉默实验组细胞中HHIP基因的表达.以2.5％、5.0％、10％浓度的香烟提取物刺激两组细胞,Western blot法检测细胞释放的IL-6、IL-8、细胞间黏附分子1的蛋白水平,实时荧光定量法检测其mRNA水平,比较两组细胞之间的差异.结果 除5％浓度香烟提取物作用下检测到的IL 6、IL8水平之外,其余浓度作用下,实验组细胞释放的炎症介质水平均高于对照组,差异有统计学意义.HHIP基因低表达时,3种炎症介质mRNA与蛋白表达较对照组都有升高,其中IL-6、IL-8较显著,而ICAM 1蛋白升高幅度相对较低.结论 HHIP基因低表达可上调炎症介质水平,从而放大气道炎症反应,其通过调节炎症介质水平对吸烟介导的气道炎症产生一定的调控作用,从而影响个体对COPD的易感性.

The roal of HHIP gene in cigarette-induced airway inflammation

Objective HHIP gene had been found associated with susceptibility to chronic obstructive pulmonary disease (COPD),but its role in cigarette-induced airway inflammation remained unclear.Our aim was to explore the role of HHIP gene in cigarette-induced airway inflammation.Methods We devided human alveolar epithelial pulmonary cells (A549) into two groups:control and HHIP gene silent cells.The later were constructed with siRNA technic.The two groups were stimulated with cigarette smoking extract (CSE) with different concentration,then we compared mRNA and protein expression level of interleukin 6、interleukin-8、intercell adhesion molecular-1 before and after using real time polymerase chain reaction and western blot.Results After CSE (2.5％、10％) stimulation for 24 h,the mRNA and protein expression level of IL-6、IL-8、intercell adhesion molecules 1 increased significantly in HHIP gene silent A549 group compared with control A549.Conclusions HHIP gene plays an important role in regulation of cigarette-induced airway inflammatory mediators levels.Deficient of the gene may lead to development of COPD.Further gene therapy needs to be investigated.