Tumor necrosis factor-α triggers mucus production in airway epithelium through an IκB kinase β-dependent mechanism
Tumor necrosis factor-α triggers mucus production in airway epithelium through an IκB kinase β-dependent mechanism
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DOI：
10.1074/jbc.m507977200
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发表时间：
2005-10-28
影响因子：
4.8
通讯作者：
Fraser, CC
中科院分区：
文献类型：
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作者：
Lora, JM;Zhang, DM;Fraser, CC
由气道上皮产生的过多粘液是许多呼吸道疾病的主要特征，包括哮喘、慢性支气管炎和囊性纤维化。然而，导致粘液产生的信号转导途径知之甚少。在此，我们研究了I κ B激酶β（IKK β）在体外和体内粘液合成中的潜在作用。肿瘤坏死因子-α（TNF-α）或转化生长因子-α刺激人上皮细胞导致粘液分泌，如MUC 5AC mRNA和蛋白质所测量。TNF-α刺激诱导IKK β依赖性p65核转位、粘液合成和上皮细胞产生细胞因子。TNF-α，而不是转化生长因子-α，诱导依赖于IKK β介导的NF-κ B活化的粘液产生。在体内，TNF-α诱导NF-κ B，如通过整个小鼠身体生物发光测定的。这种激活定位于上皮，如NF-κ B-LacZ转基因小鼠中的LacZ染色所示。TNF-α诱导的体内粘液产生也可以通过向上皮中施用IKK β显性阴性腺病毒来抑制。总之，我们的研究结果证实了IKK β在体外和体内气道上皮中TNF-α介导的粘液产生中的重要作用。
Excessive mucus production by airway epithelium is a major characteristic of a number of respiratory diseases, including asthma, chronic bronchitis, and cystic fibrosis. However, the signal transduction pathways leading to mucus production are poorly understood. Here we examined the potential role of I kappa B kinase beta (IKK beta) in mucus synthesis in vitro and in vivo. Tumor necrosis factor-alpha ( TNF-alpha) or transforming growth factor-alpha stimulation of human epithelial cells resulted in mucus secretion as measured by MUC5AC mRNA and protein. TNF-alpha stimulation induced IKK beta-dependent p65 nuclear translocation, mucus synthesis, and production of cytokines from epithelial cells. TNF-alpha, but not transforming growth factor-alpha, induced mucus production dependent on IKK beta-mediated NF-kappa B activation. In vivo, TNF-alpha induced NF-kappa B as determined by whole mouse body bioluminescence. This activation was localized to the epithelium as revealed by LacZ staining in NF-kappa B-LacZ transgenic mice. TNF-alpha-induced mucus production in vivo could also be inhibited by administration into the epithelium of an IKK beta dominant negative adenovirus. Taken together, our results demonstrated the important role of IKK beta in TNF-alpha-mediated mucus production in airway epithelium in vitro and in vivo.