Inhibition of PKR ameliorates lipopolysaccharide-induced acute lung injury by suppressing NF-κB pathway in mice

Immunopharmacology and Immunotoxicology
Yinjiao LiYan Luo

Abstract

Acute lung injury (ALI) is characterized by dramatic lung inflammation and alveolar epithelial cell death. Although protein kinase R (PKR) (double-stranded RNA-activated serine/threonine kinase) has been implicated in inflammatory response to bacterial cell wall components, whether it plays roles in lipopolysaccharide (LPS)-induced ALI remains unclear. This study was aimed to reveal whether and how PKR was involved in LPS-induced ALI pathology and the potential effects of its specific inhibitor, C16 (C13H8N4OS). During the experiment, mice received C16 (100 or 500 ug/kg) intraperitoneally 1 h before intratracheal LPS instillation. Then, whole lung lavage was collected for analysis of total protein levels and proinflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and IL-6. The lungs were tested for Western blot, transferase-mediated dUTP nick-end labeling (TUNEL) stain and immunohistochemistry. Results showed that PKR phosphorylation increased significantly after LPS instillation. Furthermore, PKR specific inhibition attenuated LPS-induced lung injury (hematoxylin and eosin stain), reduced lung protein permeability (total protein levels in whole lung lavage) and suppressed proinflammatory cy...Continue Reading

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Citations

Dec 7, 2018·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ewelina GolecBen C King
Jan 29, 2019·Frontiers in Molecular Neuroscience·Shunit Gal-Ben-AriKobi Rosenblum
Jul 6, 2019·Journal of Investigative Surgery : the Official Journal of the Academy of Surgical Research·Bin WangQin Liu
Oct 3, 2020·European Respiratory Review : an Official Journal of the European Respiratory Society·Giulia EmanuelliStefan J Marciniak
Dec 15, 2018·Physiological Reports·Rudy J ValentineHyeyoon Eo
Jul 25, 2020·Virology Journal·Yuanzhi LiuXiaoyue Chen
Jul 27, 2021·Frontiers in Immunology·Robin Smyth, Jim Sun

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