Cigarette smoke-induced impairment of autophagy in macrophages increases galectin-8 and inflammation
Abstract Cigarette smoke impairs autophagy, an intracellular protein degradation system, but the consequences of this defect have not been fully elucidated, especially in macrophages. Dysfunctional alveolar macrophages play an important role in chronic obstructive pulmonary disease (COPD). Here we s...
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Nature Portfolio
2021
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oai:doaj.org-article:53ee665d1b754109b38eb255b8f98a812021-12-02T15:23:10ZCigarette smoke-induced impairment of autophagy in macrophages increases galectin-8 and inflammation10.1038/s41598-020-79848-02045-2322https://doaj.org/article/53ee665d1b754109b38eb255b8f98a812021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-79848-0https://doaj.org/toc/2045-2322Abstract Cigarette smoke impairs autophagy, an intracellular protein degradation system, but the consequences of this defect have not been fully elucidated, especially in macrophages. Dysfunctional alveolar macrophages play an important role in chronic obstructive pulmonary disease (COPD). Here we show that galectin-8, a danger receptor that identifies damaged intracellular host vesicles and initiates autophagosome engulfment, is elevated due to activation of autophagy by cigarette smoke extract (CSE) in macrophages. CSE impaired autophagic flux in PMA-differentiated U937 macrophage-like cells, resulting in intracellular accumulation of galectin-8 and the autophagic adaptor protein NDP52. COPD patients showed elevated levels of galectin-8 and NDP52 in the lung homogenates with significant increase in the serum galectin-8 levels in patients with frequent acute exacerbations. Soluble galectin-8 induced interleukin (IL)-6 release in bronchial epithelial cells via PI3Kα signalling. Thus, increased galectin-8 due to CSE-induced impaired autophagy may be involved in the pathogenesis of COPD and may be a biomarker of this disease.Yuta KonoThomas ColleyMasako ToAndriana I. PapaioannouNicolas MercadoJonathan R. BakerYasuo ToShinji AbeKosuke HarukiKazuhiro ItoPeter J. BarnesNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021) |
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Medicine R Science Q Yuta Kono Thomas Colley Masako To Andriana I. Papaioannou Nicolas Mercado Jonathan R. Baker Yasuo To Shinji Abe Kosuke Haruki Kazuhiro Ito Peter J. Barnes Cigarette smoke-induced impairment of autophagy in macrophages increases galectin-8 and inflammation |
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Abstract Cigarette smoke impairs autophagy, an intracellular protein degradation system, but the consequences of this defect have not been fully elucidated, especially in macrophages. Dysfunctional alveolar macrophages play an important role in chronic obstructive pulmonary disease (COPD). Here we show that galectin-8, a danger receptor that identifies damaged intracellular host vesicles and initiates autophagosome engulfment, is elevated due to activation of autophagy by cigarette smoke extract (CSE) in macrophages. CSE impaired autophagic flux in PMA-differentiated U937 macrophage-like cells, resulting in intracellular accumulation of galectin-8 and the autophagic adaptor protein NDP52. COPD patients showed elevated levels of galectin-8 and NDP52 in the lung homogenates with significant increase in the serum galectin-8 levels in patients with frequent acute exacerbations. Soluble galectin-8 induced interleukin (IL)-6 release in bronchial epithelial cells via PI3Kα signalling. Thus, increased galectin-8 due to CSE-induced impaired autophagy may be involved in the pathogenesis of COPD and may be a biomarker of this disease. |
format |
article |
author |
Yuta Kono Thomas Colley Masako To Andriana I. Papaioannou Nicolas Mercado Jonathan R. Baker Yasuo To Shinji Abe Kosuke Haruki Kazuhiro Ito Peter J. Barnes |
author_facet |
Yuta Kono Thomas Colley Masako To Andriana I. Papaioannou Nicolas Mercado Jonathan R. Baker Yasuo To Shinji Abe Kosuke Haruki Kazuhiro Ito Peter J. Barnes |
author_sort |
Yuta Kono |
title |
Cigarette smoke-induced impairment of autophagy in macrophages increases galectin-8 and inflammation |
title_short |
Cigarette smoke-induced impairment of autophagy in macrophages increases galectin-8 and inflammation |
title_full |
Cigarette smoke-induced impairment of autophagy in macrophages increases galectin-8 and inflammation |
title_fullStr |
Cigarette smoke-induced impairment of autophagy in macrophages increases galectin-8 and inflammation |
title_full_unstemmed |
Cigarette smoke-induced impairment of autophagy in macrophages increases galectin-8 and inflammation |
title_sort |
cigarette smoke-induced impairment of autophagy in macrophages increases galectin-8 and inflammation |
publisher |
Nature Portfolio |
publishDate |
2021 |
url |
https://doaj.org/article/53ee665d1b754109b38eb255b8f98a81 |
work_keys_str_mv |
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