红霉素对支气管上皮细胞细胞外信号调节蛋白激酶1及转录激活蛋白-1的影响  

Effects of erythromycin on synthesis of extracellular signal-regulated protein kinase and combining activity of active protein-1 in the bronchial epithelium cells

作　　者：于亮[1] 王梅[1] 鲍文韬[1] 张利[1] 袁军[1] 

机构地区：[1]泰安市中心医院呼吸重症科,山东省271000

出　　处：《中华临床医师杂志（电子版）》2011年第5期19-22,共4页Chinese Journal of Clinicians(Electronic Edition)

摘　　要：目的探讨红霉素对支气管上皮细胞细胞外信号调节蛋白激酶1(ERK1)及转录激活蛋白-1(AP-1)活性的影响。方法将人支气管上皮细胞(16-HBE)分为4-羟基壬烯醛(4-HNE)组(10μmol/L)和对照组,4-HNE刺激细胞0.5h、2h、4h、8h及12h后,检测磷酸化c-Jun氨基末端激酶(JNK)、p38丝裂素活化蛋白激酶(MAPK)、ERK1/2及AP-1活性的变化,观察MAP激酶1(MEK1)抑制剂PD98059对4-HNE引起的AP-1结合活性的影响;观察红霉素对磷酸化ERK1、AP-1结合活性的影响。结果 4-HNE组在2h、4h、8h及12h各时间段ERK1/β-actin分别为2.1依0.4、1.8依0.4、1.6依0.6、1.3依0.8,对照组分别为4.2依0.2、4.8依0.7、4.4依0.5、4.3依0.6,两组比较差异有统计学意义(均P约0.05)。4-HNE组各时间段AP-1结合活性表达分别为90.6依2.0、85.7依2.2、78.2依2.6、70.6依1.8和64.9依4.8,对照组分别为98.6依2.1、98.7依3.4、100.1依3.8、101.3依4.2和97.4依3.6,两组比较差异有统计学意义(均P约0.05)。PD98059和红霉素可降低4-HNE引起的AP-1结合活性,红霉素增加4-HNE引起的磷酸化ERK1的表达。结论红霉素引起支气管上皮细胞ERK1磷酸化的增加,但可以抑制其AP-1的结合活性,可能与对ERK1/2下游信号传导通路的阻断有关。Objective To explore the role of erythromycin on the synthesis of extracellular signal-regulated protein kinase （ERK）and the combining activity of active protein-1 in the bronchial epithelium cells.Methods The experiment groups were divided into 10 μmol/L 4-HNE and control groups.The phosphorylation of ERK1/2,JNK,P38MAPK and the combining activity of AP-1 after 10 μmol/L 4-HNE stimulating for 0.5 h,2 h,4 h,8 h,12 h were all estimated.The effects of PD98059 on AP-1 combining activity,erythromycin on the synthesis of ERK1 and AP-1 combining activity by the 4-HNE were all detected.Results The level of phosphorylation of ERK1/β-actin in the 4-HNE groups were 2.1±0.4,1.8±0.4,1.6±0.6,1.3±0.8,and control group were 4.2±0.2,4.8±0.7,4.4±0.5,4.3±0.6 at 2 h,4 h,8 h,12 h,respectively,P〈0.05.while the AP-1 combining activity in the 4-HNE group were 90.6±2.0,85.7±2.2,78.2±2.6,70.6±1.8 and 64.9±4.8,and control group were 98.6±2.1,98.7±3.4,100.1±3.8,101.3±4.2,97.4±3.6 respectively,P〈0.05.The AP-1 combining activity was decreased after treatment with PD98059 or erythromycin before treated with 4-HNE,and the expression of phosphorylation ERK1 increased with erythromycin incubation before treated with 4-HNE.Conclusions Erythromycin could not block but increase the phosphorylation ERK1.It maybe block the downstream sites of ERK1 and decrease the AP-1combining activity.

关 键 词：红霉素 丝裂原活化蛋白激酶3 4-羟基壬烯醛 激活蛋白-1 

分 类 号：R96[医药卫生—药理学]