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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 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 PI3K? 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.

SUBMITTER: Kono Y 

PROVIDER: S-EPMC7801483 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Cigarette smoke-induced impairment of autophagy in macrophages increases galectin-8 and inflammation.

Kono Yuta Y   Colley Thomas T   To Masako M   Papaioannou Andriana I AI   Mercado Nicolas N   Baker Jonathan R JR   To Yasuo Y   Abe Shinji S   Haruki Kosuke K   Ito Kazuhiro K   Barnes Peter J PJ  

Scientific reports 20210111 1


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  ...[more]

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