【摘要】 目的探讨TGF-β在香烟烟雾提取物(cigarette smoke extract,CSE)诱导的正常人外周血中性粒细胞内质网应激(endoplasmic reticulum stress,ER stress)中的作用。方法实验分3组:正常对照组、CSE刺激组、CSE刺激+内质网应激抑制剂4-苯基丁酸(4-phenylbutyrate,4-PBA)组。培养正常人外周血中性粒细胞,给予不同浓度的CSE刺激16h,流式细胞术检测中性粒细胞GRP78、TGF-β、NF-κB、ERK、p38-MAPK的表达,ELISA法检测CXCL-8蛋白表达水平。结果 CSE增强中性粒细胞GRP78及TGF-β的表达,并在一定范围内呈浓度依赖性;内质网应激抑制剂4-PBA减少CXCL-8的分泌(P<0.05)和TGF-β的表达(P<0.05)。CSE对中性粒细胞表面NF-κB、ERK、p38-MAPK的表达无明显作用。结论 CSE诱导中性粒细胞内质网应激,并上调CXCL-8和TGF-β水平;4-PBA减少中性粒细胞分泌CXCL-8,可能与下调TGF-β表达有关。更多还原

【Abstract】 Objective To investigate the effect of TGF-βin endoplasmic reticulum stress(ER stress)of neutrophils induced by cigarette smoke extract(CSE).Methods Neutrophils were cultured and divided into 3groups:normal control group,CSEstimulation group,and CSE+4-phenylbutyrate(4-PBA)group.Neutrophils were cultured and stimulated with CSE for 16 hat concentrations of 5%,10% and 20%,respectively.GRP78,TGF-β,NF-κB,ERK and p38-MAPK were detected by flow cytometry.ELISA was performed to test the secretion of CXCL-8.Results The expression of GRP78 and TGF-βwas increased in CSE-stimulated neutrophils(P<0.05),furthermore,it was concentration-dependent in a certain range.4-PBA significantly reduced the expression of CXCL-8and TGF-β(P<0.05),in addition,CSE did not significantly affect the expression of NF-κB,ERK and p38-MAPK on neutrophils.Conclusion Cigarette smoke extract induces ER stress in neutrophils and up-regulates CXCL-8and TGF-β;4-PBA decreases secretion of CXCL-8in 4-PBA probably through down-regulating the expression of TGF-β.更多还原