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The involvement of microRNAs in macrophages' response to viruses in asthma exacerbations

The involvement of microRNAs in macrophages' response to viruses in asthma exacerbations
The involvement of microRNAs in macrophages' response to viruses in asthma exacerbations
Background: More than half of asthma exacerbations are caused by infection with human rhinovirus. When infected with rhinovirus (RV), macrophages produce tumour necrosis factor α (TNF-α), a pro-inflammatory cytokine that has been reported to be increased in the bronchoalveolar lavage of severe asthmatics. MicroRNAs thought to be involved in inflammatory responses were seen to be upregulated in alveolar macrophages of asthmatic patients.

Hypothesis: MicroRNA profile is altered in asthmatic macrophages and airway and this leads to an exaggerated pro-inflammatory response to rhinoviral infections.

Results:
MiR-27a, miR-155 and miR-152 contributed to RV-induced TNF-α overexpression in alveolar macrophages. Upregulation of these microRNAs had an effect not only the cells’ total RNA content but also polysome-bound genes, which only marginally overlapped with Targetscan 6.2 predictions. Only 24 of these genes were common to total and polysome-bound RNA. The microRNA and inflammatory profiles of these cells could be affected by the contents of bronchoalveolar lavage, in particular exosomes. Only 6% of exosomal RNA from severe asthmatic BAL is composed of microRNAs, compared to 27% in healthy controls. Dysregulated microRNAs could affect relevant pathways such as epithelial barrier, transforming growth factor β (TGF-β) and mitogen-activated protein kinases (MAPK) pathways, among others.

Conclusions: MiR-27a, miR-155 and miR-152 are upregulated in macrophages from asthmatic patients. These microRNAs are able to increase TNF-α production following RV infection which could lead to worsening of symptoms in an asthmatic exacerbation. Such dysregulation could arise from differential loading of exosomes by airway cells. In order to improve their efficacy, microRNA function studies should ally in silico prediction tools with sequencing of both total and polysome-bound RNA.
University of Southampton
Francisco Garcia, Ana Soraia
0d675d21-b92a-4d66-81b6-9f2a82545ade
Francisco Garcia, Ana Soraia
0d675d21-b92a-4d66-81b6-9f2a82545ade
Howarth, Peter
ff19c8c4-86b0-4a88-8f76-b3d87f142a21
Sanchez-Elsner, Tilman
b8799f8d-e2b4-4b37-b77c-f2f0e8e2070d

Francisco Garcia, Ana Soraia (2014) The involvement of microRNAs in macrophages' response to viruses in asthma exacerbations. University of Southampton, Doctoral Thesis, 263pp.

Record type: Thesis (Doctoral)

Abstract

Background: More than half of asthma exacerbations are caused by infection with human rhinovirus. When infected with rhinovirus (RV), macrophages produce tumour necrosis factor α (TNF-α), a pro-inflammatory cytokine that has been reported to be increased in the bronchoalveolar lavage of severe asthmatics. MicroRNAs thought to be involved in inflammatory responses were seen to be upregulated in alveolar macrophages of asthmatic patients.

Hypothesis: MicroRNA profile is altered in asthmatic macrophages and airway and this leads to an exaggerated pro-inflammatory response to rhinoviral infections.

Results:
MiR-27a, miR-155 and miR-152 contributed to RV-induced TNF-α overexpression in alveolar macrophages. Upregulation of these microRNAs had an effect not only the cells’ total RNA content but also polysome-bound genes, which only marginally overlapped with Targetscan 6.2 predictions. Only 24 of these genes were common to total and polysome-bound RNA. The microRNA and inflammatory profiles of these cells could be affected by the contents of bronchoalveolar lavage, in particular exosomes. Only 6% of exosomal RNA from severe asthmatic BAL is composed of microRNAs, compared to 27% in healthy controls. Dysregulated microRNAs could affect relevant pathways such as epithelial barrier, transforming growth factor β (TGF-β) and mitogen-activated protein kinases (MAPK) pathways, among others.

Conclusions: MiR-27a, miR-155 and miR-152 are upregulated in macrophages from asthmatic patients. These microRNAs are able to increase TNF-α production following RV infection which could lead to worsening of symptoms in an asthmatic exacerbation. Such dysregulation could arise from differential loading of exosomes by airway cells. In order to improve their efficacy, microRNA function studies should ally in silico prediction tools with sequencing of both total and polysome-bound RNA.

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Master document final print - Version of Record
Available under License University of Southampton Thesis Licence.
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Published date: September 2014

Identifiers

Local EPrints ID: 434995
URI: http://eprints.soton.ac.uk/id/eprint/434995
PURE UUID: 8765da92-82dc-4c28-a741-0de1b0600022
ORCID for Tilman Sanchez-Elsner: ORCID iD orcid.org/0000-0003-1915-2410

Catalogue record

Date deposited: 17 Oct 2019 16:30
Last modified: 23 Jul 2022 04:44

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Contributors

Author: Ana Soraia Francisco Garcia
Thesis advisor: Peter Howarth
Thesis advisor: Tilman Sanchez-Elsner ORCID iD

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