Glycogen synthase kinase-3β modulation of glucocorticoid responsiveness in COPD

American Journal of Physiology. Lung Cellular and Molecular Physiology
Anta NgkeloIrene H Heijink

Abstract

In chronic obstructive pulmonary disease (COPD), oxidative stress regulates the inflammatory response of bronchial epithelium and monocytes/macrophages through kinase modulation and has been linked to glucocorticoid unresponsiveness. Glycogen synthase-3β (GSK3β) inactivation plays a key role in mediating signaling processes upon reactive oxygen species (ROS) exposure. We hypothesized that GSK3β is involved in oxidative stress-induced glucocorticoid insensitivity in COPD. We studied levels of phospho-GSK3β-Ser9, a marker of GSK3β inactivation, in lung sections and cultured monocytes and bronchial epithelial cells of COPD patients, control smokers, and nonsmokers. We observed increased levels of phospho-GSK3β-Ser9 in monocytes, alveolar macrophages, and bronchial epithelial cells from COPD patients and control smokers compared with nonsmokers. Pharmacological inactivation of GSK3β did not affect CXCL8 or granulocyte-macrophage colony-stimulating factor (GM-CSF) expression but resulted in glucocorticoid insensitivity in vitro in both inflammatory and structural cells. Further mechanistic studies in monocyte and bronchial epithelial cell lines showed that GSK3β inactivation is a common effector of oxidative stress-induced activatio...Continue Reading

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Citations

Oct 4, 2017·American Journal of Physiology. Lung Cellular and Molecular Physiology·David E Surate SolaligueRory E Morty
Mar 9, 2021·Journal of Neuromuscular Diseases·Valentina GrandeAndreas Roos
May 8, 2021·The Journal of Pathology·Sharif MoradiMostafa Ghanei
Jun 7, 2021·Molecular Aspects of Medicine·Gaetano CaramoriIan M Adcock

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Datasets Mentioned

BETA
GM-CSF

Methods Mentioned

BETA
FCS
PCR
immunoprecipitation
ELISA
bronchoalveolar lavage
transfection

Software Mentioned

Partek
Partek Genomics Suite
COPD

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