Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/124444
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Type: Journal article
Title: MicroRNA-125a and -b inhibit A20 and MAVS to promote inflammation and impair antiviral response in COPD
Author: Hsu, A.
Dua, K.
Starkey, M.
Haw, T.
Nair, P.
Nichol, K.
Zammit, N.
Grey, S.
Baines, K.
Foster, P.
Hansbro, P.
Wark, P.
Citation: JCI insight, 2017; 2(7):e90443-e90443
Publisher: American Society for Clinical Investigation
Issue Date: 2017
ISSN: 2379-3708
2379-3708
Statement of
Responsibility: 
Alan C-Y. Hsu, Kamal Dua, Malcolm R. Starkey, Tatt-Jhong Haw, Prema M. Nair ... Shane T. Grey ... et al.
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.
Keywords: Mitochondria
Rights: JCI Insight is an open access journal. All research content is freely available immediately upon publication, and all articles published in JCI Insight are deposited in PubMed Central (PMC). Users are allowed to read, download, print, search, or link to the full texts of the articles under the "fair use" limitations of US copyright law.
DOI: 10.1172/jci.insight.90443
Grant ID: http://purl.org/au-research/grants/nhmrc/1045762
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