Oxidants and signaling by mitogen-activated protein kinasis in lung epithelium
Oxidants and signaling by mitogen-activated protein kinasis in lung epithelium
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DOI：
10.1165/rcmb.2006-0047sf
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发表时间：
2006-06-01
影响因子：
6.4
通讯作者：
Reddy, Sekhar P.
中科院分区：
文献类型：
--
作者：
Mossman, Brooke T.;Lounsbury, Karen M.;Reddy, Sekhar P.
香烟烟雾中的氧化剂和石棉纤维产生的氧化剂在体外和体内激活肺上皮细胞中的丝裂原活化蛋白激酶（MAPK）信号级联反应。这些信号通路导致Jun和Fos家族成员（即激活蛋白[AP]-1转录因子的组分）激活一些参与细胞增殖或死亡、分化和炎症的AP-1依赖性靶基因的转录能力增强。Basbaum实验室的研究表明，粘蛋白转录对香烟烟雾和革兰氏阳性细菌的反应是通过表皮生长因子受体和MAPK级联反应的激活来介导的。我们实验室的工作支持这样一个概念，即香烟烟雾和石棉引起的MAPK信号和AP-1转激活可能在肺上皮细胞损伤、肺上皮细胞代偿性增殖和癌变中协同作用，支持吸烟石棉工人肺癌发病率显著增加的机制框架。靶向MAPKs和相互关联的信号级联可能对预防肺癌和控制包括哮喘、囊性纤维化、慢性支气管炎和慢性阻塞性肺疾病在内的许多肺部疾病的粘蛋白过量产生至关重要。
Oxidants in cigarette smoke and generated from asbestos fibers activate mitogen-activated protein kinase (MAPK) signaling cascades in lung epithelial cells in vitro and in vivo. These signaling pathways lead to the enhanced ability of Jun and Fos family members (i.e., components of the activator protein [AP]-1 transcription factor) to activate transcription of a number of AP-1-dependent target genes involved in cell proliferation or death, differentiation, and inflammation. Research by the Basbaum laboratory has been critical in showing that mucin transcription in response to cigarette smoke and gram-positive bacteria is mediated through activation of the epidermal growth factor receptor and MAPK cascades. Work from our laboratories supports the concept that MAPK signaling and AP-1 transactivation by cigarette smoke and asbestos may synergize in lung epithelial cell injury, compensatory proliferation of lung epithelial cells, and carcinogenesis, supporting a mechanistic framework for the striking increases in lung cancer incidence in asbestos workers who smoke. Targeting of MAPKs and inter-related signaling cascades may be critical to the prevention of lung cancers and control of mucin overproduction in a number of lung diseases including asthma, cystic fibrosis, chronic bronchitis, and chronic obstructive pulmonary disease.