miR-146a-5p plays an essential role in the aberrant epithelial-fibroblast cross-talk in COPD.

Osei, ET; Florez-Sampedro, L; Tasena, H; Faiz, A; Noordhoek, JA; Timens, W; Postma, DS; Hackett, TL; Heijink, IH; Brandsma, C-A

miR-146a-5p plays an essential role in the aberrant epithelial-fibroblast cross-talk in COPD.

Osei, ET Florez-Sampedro, L Tasena, H Faiz, A

Noordhoek, JA Timens, W Postma, DS Hackett, TL Heijink, IH Brandsma, C-A

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Publisher:: European Respiratory Society
Publication Type:: Journal Article
Citation:: European Respiratory Journal, 2017, 49, (5), pp. 1-11
Issue Date:: 2017-05

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Field	Value	Language
dc.contributor.author	Osei, ET
dc.contributor.author	Florez-Sampedro, L
dc.contributor.author	Tasena, H
dc.contributor.author	Faiz, A https://orcid.org/0000-0003-1740-3538
dc.contributor.author	Noordhoek, JA
dc.contributor.author	Timens, W
dc.contributor.author	Postma, DS
dc.contributor.author	Hackett, TL
dc.contributor.author	Heijink, IH
dc.contributor.author	Brandsma, C-A
dc.date.accessioned	2022-07-08T01:37:55Z
dc.date.available	2017-01-29
dc.date.available	2022-07-08T01:37:55Z
dc.date.issued	2017-05
dc.identifier.citation	European Respiratory Journal, 2017, 49, (5), pp. 1-11
dc.identifier.issn	0904-1850
dc.identifier.issn	1399-3003
dc.identifier.uri	http://hdl.handle.net/10453/158744
dc.description.abstract	We previously reported that epithelial-derived interleukin (IL)-1α drives fibroblast-derived inflammation in the lung epithelial-mesenchymal trophic unit. Since miR-146a-5p has been shown to negatively regulate IL-1 signalling, we investigated the role of miR-146a-5p in the regulation of IL-1α-driven inflammation in chronic obstructive pulmonary disease (COPD).Human bronchial epithelial (16HBE14o-) cells were co-cultured with control and COPD-derived primary human lung fibroblasts (PHLFs), and miR-146a-5p expression was assessed with and without IL-1α neutralising antibody. Genomic DNA was assessed for the presence of the single nucleotide polymorphism (SNP) rs2910164. miR-146a-5p mimics were used for overexpression studies to assess IL-1α-induced signalling and IL-8 production by PHLFs.Co-culture of PHLFs with airway epithelial cells significantly increased the expression of miR-146a-5p and this induction was dependent on epithelial-derived IL-1α. miR-146a-5p overexpression decreased IL-1α-induced IL-8 secretion in PHLFs via downregulation of IL-1 receptor-associated kinase-1. In COPD PHLFs, the induction of miR-146a-5p was significantly less compared with controls and was associated with the SNP rs2910164 (GG allele) in the miR-146a-5p gene.Our results suggest that induction of miR-146a-5p is involved in epithelial-fibroblast communication in the lungs and negatively regulates epithelial-derived IL-1α induction of IL-8 by fibroblasts. The decreased levels of miR-146a-5p in COPD fibroblasts may induce a more pro-inflammatory phenotype, contributing to chronic inflammation in COPD.
dc.format	Electronic-Print
dc.language	eng
dc.publisher	European Respiratory Society
dc.relation.ispartof	European Respiratory Journal
dc.relation.isbasedon	10.1183/13993003.02538-2016
dc.rights	info:eu-repo/semantics/closedAccess
dc.subject.classification	Respiratory System
dc.subject.mesh	Alleles
dc.subject.mesh	Antibodies, Neutralizing
dc.subject.mesh	Bronchi
dc.subject.mesh	Cell Line, Tumor
dc.subject.mesh	Cigarette Smoking
dc.subject.mesh	Coculture Techniques
dc.subject.mesh	Culture Media, Conditioned
dc.subject.mesh	Epithelial Cells
dc.subject.mesh	Epithelium
dc.subject.mesh	Fibroblasts
dc.subject.mesh	Humans
dc.subject.mesh	Inflammation
dc.subject.mesh	Interleukin-1alpha
dc.subject.mesh	Interleukin-8
dc.subject.mesh	MicroRNAs
dc.subject.mesh	Polymorphism, Single Nucleotide
dc.subject.mesh	Pulmonary Disease, Chronic Obstructive
dc.subject.mesh	Signal Transduction
dc.subject.mesh	Tobacco Products
dc.subject.mesh	Alleles
dc.subject.mesh	Antibodies, Neutralizing
dc.subject.mesh	Bronchi
dc.subject.mesh	Cell Line, Tumor
dc.subject.mesh	Cigarette Smoking
dc.subject.mesh	Coculture Techniques
dc.subject.mesh	Culture Media, Conditioned
dc.subject.mesh	Epithelial Cells
dc.subject.mesh	Epithelium
dc.subject.mesh	Fibroblasts
dc.subject.mesh	Humans
dc.subject.mesh	Inflammation
dc.subject.mesh	Interleukin-1alpha
dc.subject.mesh	Interleukin-8
dc.subject.mesh	MicroRNAs
dc.subject.mesh	Polymorphism, Single Nucleotide
dc.subject.mesh	Pulmonary Disease, Chronic Obstructive
dc.subject.mesh	Signal Transduction
dc.subject.mesh	Tobacco Products
dc.subject.mesh	Bronchi
dc.subject.mesh	Epithelium
dc.subject.mesh	Cell Line, Tumor
dc.subject.mesh	Fibroblasts
dc.subject.mesh	Epithelial Cells
dc.subject.mesh	Humans
dc.subject.mesh	Pulmonary Disease, Chronic Obstructive
dc.subject.mesh	Inflammation
dc.subject.mesh	MicroRNAs
dc.subject.mesh	Interleukin-8
dc.subject.mesh	Culture Media, Conditioned
dc.subject.mesh	Coculture Techniques
dc.subject.mesh	Signal Transduction
dc.subject.mesh	Polymorphism, Single Nucleotide
dc.subject.mesh	Alleles
dc.subject.mesh	Interleukin-1alpha
dc.subject.mesh	Antibodies, Neutralizing
dc.subject.mesh	Tobacco Products
dc.subject.mesh	Cigarette Smoking
dc.title	miR-146a-5p plays an essential role in the aberrant epithelial-fibroblast cross-talk in COPD.
dc.type	Journal Article
utslib.citation.volume	49
utslib.location.activity	England
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
pubs.organisational-group	/University of Technology Sydney/Centre for Health Technologies (CHT)
utslib.copyright.status	closed_access	*
pubs.consider-herdc	false
dc.date.updated	2022-07-08T01:37:54Z
pubs.issue	5
pubs.publication-status	Published
pubs.volume	49
utslib.citation.issue	5

Abstract:

We previously reported that epithelial-derived interleukin (IL)-1α drives fibroblast-derived inflammation in the lung epithelial-mesenchymal trophic unit. Since miR-146a-5p has been shown to negatively regulate IL-1 signalling, we investigated the role of miR-146a-5p in the regulation of IL-1α-driven inflammation in chronic obstructive pulmonary disease (COPD).Human bronchial epithelial (16HBE14o-) cells were co-cultured with control and COPD-derived primary human lung fibroblasts (PHLFs), and miR-146a-5p expression was assessed with and without IL-1α neutralising antibody. Genomic DNA was assessed for the presence of the single nucleotide polymorphism (SNP) rs2910164. miR-146a-5p mimics were used for overexpression studies to assess IL-1α-induced signalling and IL-8 production by PHLFs.Co-culture of PHLFs with airway epithelial cells significantly increased the expression of miR-146a-5p and this induction was dependent on epithelial-derived IL-1α. miR-146a-5p overexpression decreased IL-1α-induced IL-8 secretion in PHLFs via downregulation of IL-1 receptor-associated kinase-1. In COPD PHLFs, the induction of miR-146a-5p was significantly less compared with controls and was associated with the SNP rs2910164 (GG allele) in the miR-146a-5p gene.Our results suggest that induction of miR-146a-5p is involved in epithelial-fibroblast communication in the lungs and negatively regulates epithelial-derived IL-1α induction of IL-8 by fibroblasts. The decreased levels of miR-146a-5p in COPD fibroblasts may induce a more pro-inflammatory phenotype, contributing to chronic inflammation in COPD.

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http://hdl.handle.net/10453/158744