期刊
EUROPEAN JOURNAL OF PHARMACOLOGY
卷 767, 期 -, 页码 135-143出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ejphar.2015.10.018
关键词
Thrombin; IL-8/CXCL8; Casein kinase 2 (CK2); Mitogen stress-activated protein kinase 1 (MSK1); p65; Lung inflammation
资金
- Taipei Medical University Hospital [102TMU-TMUH-17, 103TMU-TMUH-04]
- Ministry of Science and Technology, Taiwan [MOST 103-2320-B-038-023-MY3]
Airway inflammation plays a major role in the pathophysiology of lung inflammatory diseases such as asthma. Thrombin, a serine protease, is known to mediate central functions in thrombosis and hemostasis and also plays a critical role in lung inflammation via producing chemokine release including interleukin (IL)-8/CXCL8. Our previous studies showed that c-Src- and Rac-dependent nuclear factor (NF)-kappa B signaling pathways participate in thrombin-induced IL-8/CXCL8 release in human lung epithelial cells. In this study, we further investigated the role of casein kinase 2 (CK2)/mitogen stress-activated protein kinase 1 (MSK1)-dependent p65 phosphorylation in thrombin-induced NF-kappa B activation and IL-8/CXCL8 release. Thrombin-induced IL-8/CXCL8 release was inhibited by CK2 inhibitors (apigenin and tetrabromobenzotriazole, TBB), small interfering RNA of CK2 beta (CK2 beta siRNA), and MSK1 siRNA. Treatment of cells with thrombin caused increases in CK2 beta phosphorylation at Ser209, which was inhibited by a protein kinase C alpha (PKC alpha) inhibitor (Ro-32-0432). Thrombin-induced MSK1 phosphorylation at Ser581 and Akt phosphorylation at Ser473 were inhibited by apigenin. Moreover, the thrombin-induced increase in IL-8/CXCL8 release was attenuated by p65 siRNA. Stimulation of cells with thrombin resulted in an increase in p65 phosphorylation at 5er276, which was inhibited by apigenin and MSK1 siRNA. Thrombin-induced kappa B-luciferase activity was also inhibited by apigenin and MSK1 siRNA. Taken together, these results show that thrombin activates the PKC alpha/CK2/MSK1 signaling pathways, which in turn initiates p65 phosphorylation and NF-kappa B activation, and ultimately induces IL-8/CXCL8 release in human lung epithelial cells. (C) 2015 Elsevier B.V. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据