p300 and C/EBPβ-regulated IKKβ expression are involved in thrombin-induced IL-8/CXCL8 expression in human lung epithelial cells
| Autor: | Bing Chang Chen, Chun Ping Jiang, Gi Shih Lien, Zheng Wei Huang, Chien-Huang Lin |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
IκB kinase Respiratory Mucosa Biology Cell Line 03 medical and health sciences Thrombin medicine Humans Interleukin 8 Histone H3 acetylation Protein kinase A Lung Pharmacology Inflammation CCAAT-Enhancer-Binding Protein-beta Interleukin-8 I-Kappa-B Kinase Epithelial Cells Molecular biology I-kappa B Kinase IκBα 030104 developmental biology Gene Expression Regulation Signal transduction E1A-Associated p300 Protein medicine.drug |
| Zdroj: | Pharmacological research. 121 |
| ISSN: | 1096-1186 |
| Popis: | Asthma and chronic obstructive pulmonary disease (COPD) are common chronic lung inflammatory diseases. Thrombin and interleukin (IL)-8/C-X-C chemokine ligand 8 (CXCL8) play critical roles in lung inflammation. Our previous study showed that c-Src-dependent IκB kinase (IKK)/IκBα/nuclear factor (NF)-κB and mitogen-activated protein kinase kinase kinase 1 (MEKK1)/extracellular signal-regulated kinase (ERK)/ribosomal S6 protein kinase (RSK)-dependent CAAT/enhancer-binding protein β (C/EBPβ) activation are involved in thrombin-induced IL-8/CXCL8 expression in human lung epithelial cells. In this study, we aimed to investigate the roles of p300 and C/EBPβ-reliant IKKβ expression in thrombin-induced IL-8/CXCL8 expression. Thrombin-induced increases in IL-8/CXCL8-luciferase activity and IL-8/CXCL8 release were inhibited by p300 small interfering (siRNA). Thrombin-caused histone H3 acetylation was attenuated by p300 siRNA. Stimulation of cells with thrombin for 12h resulted in increases in IKKβ expression and phosphorylation in human lung epithelial cells. However, thrombin did not affect p65 expression. Moreover, 12h of thrombin stimulation produced increases in IKKβ expression and phosphorylation, and IκBα phosphorylation, which were inhibited by C/EBPβ siRNA. Finally, treatment of cells with thrombin caused increases in p300 and C/EBPβ complex formation, p65 and C/EBPβ complex formation, and recruitment of p300, p65, and C/EBPβ to the IL-8/CXCL8 promoter. These results imply that p300-dependent histone H3 acetylation and C/EBPβ-regulated IKKβ expression contribute to thrombin-induced IL-8/CXCL8 expression in human lung epithelial cells. Results of this study will help clarify C/EBPβ signaling pathways involved in thrombin-induced IL-8/CXCL8 expression in human lung epithelial cells. |
| Databáze: | OpenAIRE |
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