Effect of cigarette smoke extract on lipopolysaccha-ride-activated mitogen-activated protein kinase

来源 :中华医学杂志(英文版) | 被引量 : 0次 | 上传用户:Maygzs
下载到本地 , 更方便阅读
声明 : 本文档内容版权归属内容提供方 , 如果您对本文有版权争议 , 可与客服联系进行内容授权或下架
论文部分内容阅读
Background Lipopolysaccharide (LPS) forms outer membrane of the wall of Gram-negative cells. LPS can directly cause damage to epithelia of respiratory tract and is the major factor responsible for the chronic inflammation of respiratory passage. The mitogen-activated protein kinase (MAPK) signal transduction pathway of the airway epithelia is intimately associated with the action of LPS. The chronic inflammation of respiratory tract and smoking are interrelated and entwined in the development and progression of chronic lung diseases. This study was designed to examine the effects of cigarette smoke extract (CSE) and LPS on MAPK signal transduction pathway in order to further understand the roles CSE and LPS play in chronic lung inflammation.Methods Cultured primary human epithelial cells of airway were divided into four groups according to the stimulants used: blank control group, LPS-stimulation group, CSE-stimulation group and CSE plus LPS group. West blotting was employed for the detection of phosphorylation level of extracellular-signal-regulated-kinase (ERK1/2), p38 MAPK and c-Jun N-terminal kinase (JNK). The expression of cytokines of MAPK transduction pathway (granulocyte-macrophage colony stimulating factor (GM-CSF) and mRNA of IL-8) in the primary epithelial cells of respiratory tract was also determined.Results West blotting revealed that the phosphorylation levels of ERK1/2, p38 MAPK and JNK were low and 2 hours after the LPS stimulation, the phosphorylation of ERK1/2, p38 MAPK and JNK were all increased. There was a significant difference in the phosphorylation between the LPS-stimulation group and blank control group (P<0.05); no significant difference was found between CSE-stimulation group and blank control group (P>0.05); there was a significant difference between CSE + LPS group and blank control group and between CSE + LPS group and LPS group (P<0.05). The phosphorylation of CSE-LPS group was higher than that of blank control group but lower than that of LPS group. In blank control group, the expression of IL-8 and GM-CSF mRNA was low in the epithelial cells of airway and the release of IL-8 and GM-CSF was also at a low level. One hour after LPS stimulation, the level of IL-8 mRNA increased (P<0.05) and reached a peak after 2 hours. On the other hand, GM-CSF mRNA level increased 2 hours after the stimulation (P<0.05)and reached the highest level 4 hours after the stimulation. Two hours after LPS stimulation, IL-8 and GM-CSF protein level began to rise (P<0.05), and the level was the highest 8 hours after the stimulation (P<0.01). Stimulation with CSE alone had no effect on the release of IL-8 and GM-CSF and expression of IL-8 mRNA (P>0.05), but pre-treatment with CSE could delay the LPS-induced release of IL-8 and GM-CSF and the expression of IL-8 mRNA and its peak was lower.Conclusions LPS stimulation can significantly increase the phosphorylation of ERK1/2, p38 MAPK and JNK in the epithelial cells of airway and activate the MAPK transduction pathway, thereby can activate the downstream signal transduction pathway, and can ultimately result in the release of cytokines by the epithelial cells of airway. CSE can partially abolish the LPS-induced activation of MAPK signal transduction pathway and the expression of cytokines of the pathway, which might contribute to the development and progression of the inflammatory reactions in COPD patients.
其他文献
该文首先介绍了制浆造纸系统中树脂沉积物的组成和来源,然后阐述了树脂沉积的 机理和评价方法,最后对制浆造纸系统中树脂沉积的控制方法(尤其是化学控制法和 生物控制法)进行了
期刊
2009年4月16日,中国共产党中国黄金集团公司第二次代表大会在北京召开。这次大会是在广大党员和全体职工深入学习实践科学发展观,全面推动集团公司总体发展战略的形势下召开的
目的 评价盘龙七片治疗膝骨性关节炎的疗效.方法 2005年10月至2007年10月收治74例膝关节骨性关节炎患者随机分为盘龙七治疗组和双氯芬酸钠对照组.治疗组予以口服盘龙七片,3片
Background Many studies have examined gender related differences in the presenting symptoms, management and prognosis of patients with acute coronary syndrome (
目的探讨番茄红素联合α-生育酚对晶状体氧化损伤进行药物治疗的可行性。方法体外培养正常大鼠晶状体,按随机分组原则将大鼠晶状体分为以下8组:空白对照组(A),过氧化氢处理组