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Cyclic stretch upregulates interleukin-8 and transforming growth factor-beta1 production through a protein kinase C-dependent pathway in alveolar epithelial cells
Authors:Yamamoto Hiroyuki  Teramoto Hidemi  Uetani Kohsaku  Igawa Katsutoshi  Shimizu Eiji
Institution:Third Department of Internal Medicine, Faculty of Medicine, Tottori University, Yonago, Japan.
Abstract:OBJECTIVE: Positive-pressure mechanical ventilation can injure the lung, causing oedema and alveolar inflammation, which is termed 'ventilator-induced lung injury' (VILI). We postulated that cyclic stretch upregulates the release of cytokines, which may cause lung damage, and explored which cytokines were released after cyclic stretch in type II alveolar epithelial cells (A549). METHODOLOGY: To test this hypothesis, A549 cells were cultured on a silicoelastic membrane and interleukin (IL)-1beta, IL-8, granulocyte-macrophage colony stimulating factor, activin, transforming growth factor (TGF)-beta1, insulin-like growth factor-2 and tumour necrosis factor-alpha mRNA and protein were assessed after stimulation of the cells by cyclic stretch. RESULTS: Cyclic stretch induced activation of protein kinase C and resulted in the release of IL-8 and TGF-beta1 from A549 cells. CONCLUSIONS: The release of IL-8 and TGF-beta1 from alveolar epithelial cells may be a contributing factor in alveolitis associated with VILI.
Keywords:alveolar epithelial cells  cyclic stretch  interleukin-8  protein kinase C  transforming growth factor-β1  ventilator-induced lung injury
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