Activation of the Heat Shock Response Attenuates the Interleukin 1β–Mediated Inhibition of the Amiloride-Sensitive Alveolar Epithelial Ion Transport
| Autor: | Marybeth Howard, Karen E. Iles, Jérémie Roux, Dale A. Dickinson, Arnaud Goolaerts, Sarah C. Christiaans, Jean-Francois Pittet, Byron Miyazawa, Michael A. Matthay, Naseem Anjum |
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| Rok vydání: | 2013 |
| Předmět: |
Male
Epithelial sodium channel Messenger Interleukin-1beta IRAK-1 Critical Care and Intensive Care Medicine Macrocyclic Amiloride Benzoquinones 2.1 Biological and endogenous factors Aetiology Lung biology LIM Domain Proteins MAP Kinase Kinase Kinases Hsp90 Up-Regulation Cell biology DNA-Binding Proteins Interleukin-1 Receptor-Associated Kinases Emergency Medicine medicine.drug Lactams MAP Kinase Signaling System Lactams Macrocyclic p38 mitogen-activated protein kinases Acute Lung Injury Clinical Sciences Respiratory Mucosa Lung injury Article stress protein response alpha ENaC TAK-1 Heat shock protein Epithelial Sodium Channel Blockers medicine Animals HSP70 Heat-Shock Proteins RNA Messenger Heat shock Epithelial Sodium Channels Emergency & Critical Care Medicine Molecular biology p38 MAP kinase Rats Hsp70 Pulmonary Alveoli Cytoskeletal Proteins biology.protein RNA Heat-Shock Response |
| Zdroj: | Shock (Augusta, Ga.), vol 39, iss 2 |
| ISSN: | 1073-2322 |
| Popis: | Acute lung injury (ALI) is a clinical syndrome characterized by hypoxia, which is caused by the breakdown of the alveolar capillary barrier. Interleukin 1β (IL-1β), a cytokine released within the airspace in ALI, downregulates the α subunit of the epithelial sodium channel (αENaC) transcription and protein expression via p38 MAP kinase-dependent signaling. Although induction of the heat shock response can restore alveolar fluid clearance compromised by IL-1β following the onset of severe hemorrhagic shock in rats, the mechanisms are not fully understood. In this study, we report that the induction of the heat shock response prevents IL-1β-dependent inhibition of αENaC mRNA expression and subsequent channel function. Heat shock results in IRAK1 detergent insolubility and a disruption of Hsp90 binding to IRAK1. Likewise, TAK1, another client protein of Hsp90 and signaling component of the IL-1β pathway, is also detergent insoluble after heat shock. Twenty-four hours after heat shock, both IRAK1 and TAK1 are again detergent soluble, which correlates with the IL-1β-dependent p38 activation. Remarkably, IL-1β-dependent p38 activation 24 h after heat shock did not result in an inhibition of αENaC mRNA expression and channel function. Further analysis demonstrates prolonged preservation of αENaC expression by the activation of the heat shock response that involves inducible Hsp70. Inhibition of Hsp70 at 24 h after heat shock results in p38-dependent IL-1β inhibition of αENaC mRNA expression, whereas overexpression of Hsp70 attenuates the p38-dependent IL-1β inhibition of αENaC mRNA expression. These studies demonstrate new mechanisms by which the induction of the heat shock response protects the barrier function of the alveolar epithelium in ALI. |
| Databáze: | OpenAIRE |
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