Journal
EUROPEAN JOURNAL OF PHARMACOLOGY
Volume 767, Issue -, Pages 135-143Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ejphar.2015.10.018
Keywords
Thrombin; IL-8/CXCL8; Casein kinase 2 (CK2); Mitogen stress-activated protein kinase 1 (MSK1); p65; Lung inflammation
Categories
Funding
- Taipei Medical University Hospital [102TMU-TMUH-17, 103TMU-TMUH-04]
- Ministry of Science and Technology, Taiwan [MOST 103-2320-B-038-023-MY3]
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available