The role of miR-155 in cigarette smoke-induced pulmonary inflammation and COPD

Chronic obstructive pulmonary disease (COPD) is a highly prevalent respiratory disease characterized by airflow limitation and chronic inflammation. MiR-155 is described as an ancient regulator of the immune system. Our objective was to establish a role for miR-155 in cigarette smoke (CS)-induced in...

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Bibliographic Details
Published in:Mucosal immunology 2020-05, Vol.13 (3), p.423-436
Main Authors: De Smet, E G, Van Eeckhoutte, H P, Avila Cobos, F, Blomme, E, Verhamme, F M, Provoost, S, Verleden, S E, Venken, K, Maes, T, Joos, G F, Mestdagh, P, Brusselle, G G, Bracke, K R
Format: Article
Language:English
Subjects:
Alveoli
Animals
Chronic obstructive pulmonary disease
Cigarette smoke
Cigarette Smoking - adverse effects
Cytokines - metabolism
Disease Models, Animal
Disease Susceptibility
Elastase
Emphysema
Female
Flow cytometry
Gene expression
Gene Expression Profiling
Gene Expression Regulation
Health risk assessment
Humans
Immune system
Inflammation
Inflammation Mediators - metabolism
Lung diseases
Macrophages
Macrophages, Alveolar - immunology
Macrophages, Alveolar - metabolism
Male
Mice
Mice, Knockout
MicroRNAs - genetics
miRNA
Obstructive lung disease
Pneumonia - etiology
Pulmonary Disease, Chronic Obstructive - etiology
Pulmonary Emphysema - etiology
Pulmonary Emphysema - metabolism
Pulmonary Emphysema - pathology
Respiratory diseases
RNA Interference
Therapeutic targets
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Summary:Chronic obstructive pulmonary disease (COPD) is a highly prevalent respiratory disease characterized by airflow limitation and chronic inflammation. MiR-155 is described as an ancient regulator of the immune system. Our objective was to establish a role for miR-155 in cigarette smoke (CS)-induced inflammation and COPD. We demonstrate increased miR-155 expression by RT-qPCR in lung tissue of smokers without airflow limitation and patients with COPD compared to never smokers and in lung tissue and alveolar macrophages of CS-exposed mice compared to air-exposed mice. In addition, we exposed wild type and miR-155 deficient mice to CS and show an attenuated inflammatory profile in the latter. Alveolar macrophages were sorted by FACS from the different experimental groups and their gene expression profile was analyzed by RNA sequencing. This analysis revealed increased expression of miR-155 targets and an attenuation of the CS-induced increase in inflammation-related genes in miR-155 deficient mice. Moreover, intranasal instillation of a specific miR-155 inhibitor attenuated the CS-induced pulmonary inflammation in mice. Finally, elastase-induced emphysema and lung functional changes were significantly attenuated in miR-155 deficient mice. In conclusion, we highlight a role for miR-155 in CS-induced inflammation and the pathogenesis of COPD, implicating miR-155 as a new therapeutic target in COPD.
ISSN:1933-0219
1935-3456
DOI:10.1038/s41385-019-0241-6