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

Abstract：

: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.

journal_name

Mucosal Immunol

journal_title

Mucosal immunology

authors

De Smet EG,Van Eeckhoutte HP,Avila Cobos F,Blomme E,Verhamme FM,Provoost S,Verleden SE,Venken K,Maes T,Joos GF,Mestdagh P,Brusselle GG,Bracke KR

doi

10.1038/s41385-019-0241-6

subject

Has Abstract

pub_date

2020-05-01 00:00:00

pages

423-436

issue

3

eissn

1933-0219

issn

1935-3456

pii

10.1038/s41385-019-0241-6

journal_volume

13

pub_type

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