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Inflammation and emphysema in cigarette smoke-exposed mice when instilled with poly (I:C) or infected with influenza A or respiratory syncytial viruses

Author:
Mebratu, Yohannes A., Smith, Kevin R., Agga, Getahun E., Tesfaigzi, Yohannes
Source:
Respiratory Research 2016 v.17 no.1 pp. 75-87
ISSN:
1465-993X
Subject:
Influenza A virus, air, animal disease models, cigarettes, double-stranded RNA, gene expression, inflammation, influenza, interleukin-17, interleukin-18, interleukin-1beta, lungs, lymphocytes, macrophages, messenger RNA, mice, neutrophils, pulmonary emphysema, viruses
Abstract:
Background: The length of time for cigarette smoke (CS) exposure to cause emphysema in mice is drastically reduced when CS exposure is combined with viral infection. However, the extent of inflammatory responses and lung pathologies of mice exposed to CS and infected with influenza A virus (IAV), respiratory syncytial virus (RSV), or treated with the viral derivative dsRNA (polyinosine-polycytidylic acid [poly (I:C)] have not been compared. Methods: Mice were exposed to CS or filtered air for 4 weeks and received a single dose of vehicle, AV, or RSV infection and extent of inflammation and emphysema was evaluated 14 d later. In another set of experiments, mice were instilled with poly (I:C) twice a week during the third and fourth weeks of CS exposure and immediately analyzed for extent of inflammation and lung pathologies. Results: In CS-exposed mice, inflammation was characterized mainly by macrophages, lymphocytes, and neutrophils after IAV infection, mainly by lymphocytes, and neutrophils after RSV infection, and mainly by lymphocytes and neutrophils after poly (I:C) instillations. Despite increased inflammation, extent of emphysema by poly (I:C) was very mild; but was robust and similar for both IAV and RSV infections with enhanced MMP-12 mRNA expression and TUNEL positivity. Both IAV and RSV infections increased the levels of IL-17, IL-1β, IL-12b, IL-18, IL-23a, Ccl-2, Ccl-7 mRNAs in the lungs of CS-exposed mice with IAV causing more increases than RSV. Conclusion: CS-induced inflammatory responses and extent of emphysematous changes differ depending on the type of viral infection. These animal models may be useful to study the mechanisms by which different viruses exacerbate CS-induced inflammation and emphysema.
Agid:
5700731
Handle:
10113/5700731