PT  - JOURNAL ARTICLE
AU  - Alen Faiz
AU  - Katrina Steiling
AU  - Mirjam P. Roffel
AU  - Dirkje S. Postma
AU  - Avrum Spira
AU  - Marc E. Lenburg
AU  - Malte Borggrewe
AU  - Tim R. Eijgenraam
AU  - Marnix R. Jonker
AU  - Gerard H. Koppelman
AU  - Simon D. Pouwels
AU  - Gang Liu
AU  - Yuriy O. Alekseyev
AU  - Stephen Lam
AU  - Pieter S. Hiemstra
AU  - Peter J. Sterk
AU  - Wim Timens
AU  - Corry-Anke Brandsma
AU  - Irene H. Heijink
AU  - Maarten van den Berge
TI  - Effect of long-term corticosteroid treatment on microRNA and gene-expression profiles in Chronic Obstructive Pulmonary Disease
AID  - 10.1183/13993003.01202-2018
DP  - 2019 Jan 01
TA  - European Respiratory Journal
PG  - 1801202
4099  - http://erj.ersjournals.com/content/early/2019/01/30/13993003.01202-2018.short
4100  - http://erj.ersjournals.com/content/early/2019/01/30/13993003.01202-2018.full
AB  - To investigate whether microRNA (miRNA) expression is modulated by inhaled corticosteroid (ICS) treatment, we performed genome-wide miRNA analysis on bronchial biopsies of 69 moderate/severe COPD patients at baseline and after 6- and 30-month treatment with the ICS fluticasone propionate (FP) or placebo. The effect of ICS on miRNA expression was validated in differentiated primary bronchial epithelial cultures, and functional studies were conducted in BEAS-2B cells. MiRNAs affected by ICS and their predicted targets were compared to an independent miRNA dataset of bronchial brushings from COPD patients and healthy controls. Treatment with ICS for both 6- and 30-months significantly altered the expression of 4 miRNAs, including miR-320d, which was increased during ICS treatment compared with placebo. The ICS-induced increase of miR-320d was confirmed in primary airway epithelial cells. MiR-320d negatively correlated targets were enriched for pro-inflammatory genes and were increased in the bronchial brushes of patients with lower lung function in the independent dataset. Overexpression of miR-320d in BEAS-2B cells dampened cigarette smoke extract-induced pro-inflammatory activity via inhibition of nuclear factor (NF)-κB. Collectively, we identified miR-320d as a novel mediator of ICS, regulating the pro-inflammatory response of the airway epithelium.FootnotesThis manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.Conflict of interest: Alen FaizConflict of interest: Dr. Steiling has a patent “Biomarkers of COPD disease activity” pending.Conflict of interest: P. RoffelConflict of interest: S. PostmaConflict of interest: Avrum SpiraConflict of interest: E. LenburgConflict of interest: Malte BorggreweConflict of interest: R. EijgenraamConflict of interest: R. JonkerConflict of interest: H. KoppelmanConflict of interest: D. PouwelsConflict of interest: Gang LiuConflict of interest: Dr. Alekseyev has nothing to disclose.Conflict of interest: Stephen LamConflict of interest: S. HiemstraConflict of interest: Dr. Sterk reports grants from GlaxoSmithKline, grants from Dutch Government, during the conduct of the study.Conflict of interest: Wim TimensConflict of interest: Corry-Anke BrandsmaConflict of interest: H. HeijinkConflict of interest: Maarten van den Berge