Effect of hypoxia and dexamethasone on inflammation and ion transporter function in pulmonary cells

• Published in: Clinical and experimental immunology Vol. 169; no. 2; pp. 119 - 128
• Main Authors: Urner, M., Herrmann, I. K., Booy, C., Roth‐Z' Graggen, B., Maggiorini, M., Beck‐Schimmer, B.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.08.2012; Blackwell; Oxford University Press; Blackwell Science Inc
• Subjects: Altitude; Alveolar Epithelial Cells - drug effects; Alveolar Epithelial Cells - immunology; Alveolar Epithelial Cells - metabolism; Alveoli; Analytical, structural and metabolic biochemistry; Animals; Biological and medical sciences; Cell Hypoxia; Cell Survival - drug effects; cytokines and chemokines; Dexamethasone; Dexamethasone - pharmacology; Edema; Endothelial cells; Endothelial Cells - drug effects; Endothelial Cells - immunology; Endothelial Cells - metabolism; Epithelial cells; Fundamental and applied biological sciences. Psychology; Gene expression; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit - metabolism; Inflammation; Inflammation - immunology; Inflammation - metabolism; Inflammation Mediators - metabolism; Interleukin 6; ion channels; Ion Channels - metabolism; Ions; Leukocytes (neutrophilic); Lung; lung oedema; Macrophages; Macrophages, Alveolar - drug effects; Macrophages, Alveolar - immunology; Macrophages, Alveolar - metabolism; Monocyte chemoattractant protein 1; Original; Oxygen; Pulmonary arteries; Pulmonary artery; Rats; Rodents; Sodium; Sodium channels; Corticosteroid; Oxygen; Dexamethasone; Steroid hormone; Lung; Cytokine; Biochemistry; Ionic channel; Inflammation; Respiratory system; ion channels; Chemokine; lung oedema; Hypoxia; Cell; cytokines and chemokines
• ISSN: 0009-9104; 1365-2249
• DOI: 10.1111/j.1365-2249.2012.04595.x

Summary Dexamethasone has been found to reduce the incidence of high‐altitude pulmonary oedema. Mechanisms explaining this effect still remain unclear. We assessed the effect of dexamethasone using established cell lines, including rat alveolar epithelial cells (AEC), pulmonary artery endothelial cells (RPAEC) and alveolar macrophages (MAC), in an environment of low oxygen, simulating a condition of alveolar hypoxia as found at high altitude. Inflammatory mediators and ion transporter expression were quantified. Based on earlier results, we hypothesized that hypoxic conditions trigger inflammation. AEC, RPAEC and MAC, pre‐incubated for 1 h with or without dexamethasone (10−7 mol/l), were subsequently exposed to mild hypoxia (5% O2, or normoxia as control) for 24 h. mRNA and protein levels of cytokine‐induced neutrophil chemoattractant‐1, monocyte chemoattractant protein‐1 and interleukin‐6 were analysed. mRNA expression and functional activity of the apical epithelial sodium channel and basolateral Na+/K+‐ATPase were determined using radioactive marker ions. In all three types of pulmonary cells hypoxic conditions led to an attenuated secretion of inflammatory mediators, which was even more pronounced in dexamethasone pretreated samples. Function of Na+/K+‐ATPase was not significantly influenced by hypoxia or dexamethasone, while activity of epithelial sodium channels was decreased under hypoxic conditions. When pre‐incubated with dexamethasone, however, transporter activity was partially maintained. These findings illustrate that long‐term hypoxia does not trigger an inflammatory response. The ion transport across apical epithelial sodium channels under hypoxic conditions is ameliorated in cells treated with dexamethasone.