MicroRNA-125a and -b inhibit A20 and MAVS to promote inflammation and impair antiviral response in COPD

Hsu, ACY; Dua, K; Starkey, MR; Haw, TJ; Nair, PM; Nichol, K; Zammit, N; Grey, ST; Baines, KJ; Foster, PS; Hansbro, PM; Wark, PA

MicroRNA-125a and -b inhibit A20 and MAVS to promote inflammation and impair antiviral response in COPD

Hsu, ACY Dua, K

Starkey, MR Haw, TJ Nair, PM Nichol, K Zammit, N Grey, ST Baines, KJ Foster, PS Hansbro, PM

Wark, PA

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Publication Type:: Journal Article
Citation:: JCI insight, 2017, 2 (7), pp. e90443 - ?
Issue Date:: 2017-04-06

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Field	Value	Language
dc.contributor.author	Hsu, ACY	en_US
dc.contributor.author	Dua, K https://orcid.org/0000-0002-7507-1159	en_US
dc.contributor.author	Starkey, MR	en_US
dc.contributor.author	Haw, TJ	en_US
dc.contributor.author	Nair, PM	en_US
dc.contributor.author	Nichol, K	en_US
dc.contributor.author	Zammit, N	en_US
dc.contributor.author	Grey, ST	en_US
dc.contributor.author	Baines, KJ	en_US
dc.contributor.author	Foster, PS	en_US
dc.contributor.author	Hansbro, PM https://orcid.org/0000-0002-4741-3035	en_US
dc.contributor.author	Wark, PA	en_US
dc.date.issued	2017-04-06	en_US
dc.identifier.citation	JCI insight, 2017, 2 (7), pp. e90443 - ?	en_US
dc.identifier.uri	http://hdl.handle.net/10453/126214
dc.description.abstract	Influenza A virus (IAV) infections lead to severe inflammation in the airways. Patients with chronic obstructive pulmonary disease (COPD) characteristically have exaggerated airway inflammation and are more susceptible to infections with severe symptoms and increased mortality. The mechanisms that control inflammation during IAV infection and the mechanisms of immune dysregulation in COPD are unclear. We found that IAV infections lead to increased inflammatory and antiviral responses in primary bronchial epithelial cells (pBECs) from healthy nonsmoking and smoking subjects. In pBECs from COPD patients, infections resulted in exaggerated inflammatory but deficient antiviral responses. A20 is an important negative regulator of NF-κB-mediated inflammatory but not antiviral responses, and A20 expression was reduced in COPD. IAV infection increased the expression of miR-125a or -b, which directly reduced the expression of A20 and mitochondrial antiviral signaling (MAVS), and caused exaggerated inflammation and impaired antiviral responses. These events were replicated in vivo in a mouse model of experimental COPD. Thus, miR-125a or -b and A20 may be targeted therapeutically to inhibit excessive inflammatory responses and enhance antiviral immunity in IAV infections and in COPD.	en_US
dc.relation.ispartof	JCI insight	en_US
dc.relation.isbasedon	10.1172/jci.insight.90443	en_US
dc.subject.mesh	Cells, Cultured	en_US
dc.subject.mesh	Mitochondria	en_US
dc.subject.mesh	Epithelial Cells	en_US
dc.subject.mesh	Animals	en_US
dc.subject.mesh	Mice, Inbred BALB C	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Influenza A virus	en_US
dc.subject.mesh	Pulmonary Disease, Chronic Obstructive	en_US
dc.subject.mesh	Inflammation	en_US
dc.subject.mesh	Proteins	en_US
dc.subject.mesh	NF-kappa B	en_US
dc.subject.mesh	MicroRNAs	en_US
dc.subject.mesh	Case-Control Studies	en_US
dc.subject.mesh	Smoking	en_US
dc.subject.mesh	Virus Replication	en_US
dc.subject.mesh	Aged	en_US
dc.subject.mesh	Middle Aged	en_US
dc.subject.mesh	Female	en_US
dc.subject.mesh	Male	en_US
dc.subject.mesh	Influenza, Human	en_US
dc.subject.mesh	Intracellular Signaling Peptides and Proteins	en_US
dc.title	MicroRNA-125a and -b inhibit A20 and MAVS to promote inflammation and impair antiviral response in COPD	en_US
dc.type	Journal Article
utslib.citation.volume	7	en_US
utslib.citation.volume	2	en_US
utslib.for	1101 Medical Biochemistry and Metabolomics	en_US
pubs.embargo.period	Not known	en_US
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/Graduate School of Health
utslib.copyright.status	open_access
pubs.issue	7	en_US
pubs.publication-status	Published	en_US
pubs.volume	2	en_US

Abstract:

Influenza A virus (IAV) infections lead to severe inflammation in the airways. Patients with chronic obstructive pulmonary disease (COPD) characteristically have exaggerated airway inflammation and are more susceptible to infections with severe symptoms and increased mortality. The mechanisms that control inflammation during IAV infection and the mechanisms of immune dysregulation in COPD are unclear. We found that IAV infections lead to increased inflammatory and antiviral responses in primary bronchial epithelial cells (pBECs) from healthy nonsmoking and smoking subjects. In pBECs from COPD patients, infections resulted in exaggerated inflammatory but deficient antiviral responses. A20 is an important negative regulator of NF-κB-mediated inflammatory but not antiviral responses, and A20 expression was reduced in COPD. IAV infection increased the expression of miR-125a or -b, which directly reduced the expression of A20 and mitochondrial antiviral signaling (MAVS), and caused exaggerated inflammation and impaired antiviral responses. These events were replicated in vivo in a mouse model of experimental COPD. Thus, miR-125a or -b and A20 may be targeted therapeutically to inhibit excessive inflammatory responses and enhance antiviral immunity in IAV infections and in COPD.

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http://hdl.handle.net/10453/126214