Involvement of Syk kinase in TNF-induced nitric oxide production by airway epithelial cells.
Involvement of Syk kinase in TNF-induced nitric oxide production by airway epithelial cells.
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Syk 激酶参与 TNF 诱导的气道上皮细胞一氧化氮的产生。
DOI：
10.1016/j.bbrc.2006.10.073
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发表时间：
2006
影响因子：
3.1
通讯作者：
Befus,ADean
中科院分区：
文献类型：
--
作者：
Ulanova,Marina;Marcet-Palacios,Marcelo;Muñoz,Samira;Asfaha,Samuel;Kim,Moo-Kyung;Schreiber,AlanD;Befus,ADean
我们最近发现Syk在肺上皮细胞（EC）中广泛表达并参与β1整合素信号转导。在这项研究中，我们评估了Syk在调节NO产生中的作用。TNF刺激人支气管EC系HS-24引起诱导型一氧化氮合酶（iNOS）的表达增加。使用siRNA或Piceatannol抑制Syk下调iNOS表达并减少NO产生。这种效应发生在通过β1整合素同时刺激的EC中，表明TNF和β1整合素提供共刺激信号。抑制Syk下调TNF诱导的p38和p44/42 MAPK磷酸化和p65 NF-κB核转位。因此，TNF诱导的EC中促炎信号传导的激活导致iNOS表达增强和NO产生依赖于Syk。Syk介导的信号转导至少部分地通过激活MAPK级联来调节NO的产生。了解Syk在气道EC中的作用可能有助于开发炎性肺病的新治疗工具。
We have recently found that Syk is widely expressed in lung epithelial cells (EC) and participates in β1 integrin signaling. In this study, we assessed the role of Syk in regulation of NO production. Stimulation of human bronchial EC line HS-24 by TNF caused an increased expression of inducible nitric oxide synthase (iNOS). Inhibition of Syk using siRNA or piceatannol down-regulated the iNOS expression and reduced NO production. This effect occurred in EC simultaneously stimulated via β1 integrins, suggesting that TNF and β1 integrins provide co-stimulatory signals. Inhibition of Syk down-regulated TNF-induced p38 and p44/42 MAPK phosphorylation and nuclear translocation of p65 NF-κB. Thus, TNF-induced activation of pro-inflammatory signaling in EC leading to enhanced expression of iNOS and NO production was dependent on Syk. Syk-mediated signaling regulates NO production at least partly via activating the MAPK cascade. Understanding the role of Syk in airway EC may help in developing new therapeutic tools for inflammatory lung disorders.