P300 and C/EBPβ-regulated IKKβ expression are involved in thrombin-induced IL-8/CXCL8 expression in human lung epithelial cells. (July 2017)

• Record Type: Journal Article
• Authors: Huang, Zheng-Wei; Lien, Gi-Shih; Lin, Chien-Huang; Jiang, Chun-Ping; Chen, Bing-Chang
• Is Part Of: Pharmacological research. Volume 121(2017:Jul.)
• Page Start: 33
• Page End: 41
• Publication Date: 2017-07
• Subjects: BALF bronchoalveolar lavage fluid -- C/EBPβ CAAT/enhancer binding protein -- DMEM Dulbecco's modified Eagle's medium -- ECL enhanced chemiluminescence -- FBS fetal bovine serum -- FCS fetal calf serum -- HRP horseradish peroxidase -- IKK IκB kinase -- MEKK mitogen-activated protein kinase kinase kinase -- NF-κB nuclear factor-κB -- PAR protease-activated receptors -- PCR polymerase chain reaction -- PGE2 prostaglandin E2 -- SDS-PAGE sodium dodecylsulfate-polyacrylamide gel electrophoresis -- siRNA small interfering RNA; Chronic lung inflammatory diseases -- Thrombin -- IL-8/CXCL8 -- p300 -- CAAT/enhancer binding protein β (C/EBPβ) -- Nuclear factor-κB (NF-κB) -- Human lung epithelial cells; Pharmacology -- Periodicals; Pharmacology -- Periodicals; Research -- Periodicals; Médicaments -- Recherche -- Périodiques; Pharmacologie -- Périodiques; 615.105
• DOI: 10.1016/j.phrs.2017.04.020
• Languages: English
• ISSNs: 1043-6618

Abstract

Graphical abstract: Abstract: 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 12 h resulted in increases in IKKβ expression and phosphorylation in human lung epithelial cells. However, thrombin did not affect p65 expression. Moreover, 12 h 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.