CCAAT/Enhancer-binding Protein and Activator Protein-1 Transcription Factors Regulate the Expression of Interleukin-8 through the Mitogen-activated Protein Kinase Pathways in Response to Mechanical Stretch of Human Airway Smooth Muscle Cells (original) (raw)
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American journal of physiology. Lung cellular and molecular physiology, 2016
Ventilator-induced Lung Injury (VILI) is associated with activated inflammatory signaling such as cytokine production by endothelial, epithelial cells and macrophages, although the precise mechanisms of inflammatory activation induced by VILI-relevant cyclic stretch remain poorly understood. We show that exposure of human pulmonary endothelial cells (EC) to chronic cyclic stretch at 18% linear distension (18% CS), but not at physiologically relevant 5% CS, induces "EC activated phenotype", which was characterized by time-dependent increase in ICAM1 and VCAM1 expression. 18% CS increased in a time-dependent fashion the release of soluble ICAM1 (sICAM1) and IL-8. Investigation of potential signaling mechanisms of CS-induced EC inflammatory activation showed that 18% CS, but not 5% CS induced time-dependent upregulation of VEGF receptor 2 (VEGFR2). Both, CS-induced VEGFR2 expression and tyrosine phosphorylation was abrogated by co-treatment with ROS inhibitor, N-acetyl cystei...
Interleukin-8: novel roles in human airway smooth muscle cell contraction and migration
AJP: Cell Physiology, 2006
In patients with cystic fibrosis (CF) and asthma, elevated levels of interleukin-8 (IL-8) are found in the airways. IL-8 is a CXC chemokine that is a chemoattractant for neutrophils through CXCR1 and CXCR2 G protein-coupled receptors. We hypothesized that IL-8 acts directly on airway smooth muscle cells (ASMC) in a way that may contribute to the enhanced airway responsiveness and airway remodeling observed in CF and asthma. The aim of this study was to determine whether human ASMC (HASMC) express functional IL-8 receptors (CXCR1 and CXCR2) linked to cell contraction and migration. Experiments were conducted on cells harvested from human lung specimens. Real-time PCR and fluorescence-activated cell sorting analysis showed that HASMC expressed mRNA and protein for both CXCR1 and CXCR2. Intracellular Ca2+ concentration ([Ca2+]i) increased from 115 to 170 nM in response to IL-8 (100 nM) and decreased after inhibition of phospholipase C (PLC) with U-73122. On blocking the receptors with ...