Journal
ISCIENCE
Volume 24, Issue 10, Pages -Publisher
CELL PRESS
DOI: 10.1016/j.isci.2021.103201
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Funding
- Japan Society [19K08618]
- Grants-in-Aid for Scientific Research [19K08618] Funding Source: KAKEN
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RSV infection can exacerbate allergic airway inflammation through the production of MMP-12 by alveolar macrophages. Targeting MMP-12 may offer a potential novel therapeutic strategy for asthma exacerbation.
Respiratory syncytial virus (RSV) infection often exacerbates bronchial asthma, but there is no licensed RSV vaccine or specific treatments. Here we show that RSV-induced alveolar macrophages, which produce high levels of matrix metalloproteinase-12 (MMP-12), exacerbate allergic airway inflammation with increased neutrophil infiltration. When mice subjected to allergic airway inflammation via exposure to the house dust mite antigen (HDM) were infected with RSV (HDM/RSV), MMP-12 expression, viral load, neutrophil infiltration, and airway hyperresponsiveness (AHR) were increased compared to those in the HDM and RSV groups. These exacerbations in the HDM/RSV group were attenuated in MMP12- deficient mice and mice treated with MMP408, a selective MMP-12 inhibitor, but not in mice treated with dexamethasone. Finally, M2-like macrophages produced MMP-12, and its production was promoted by increase of IFN-beta-induced IL-4 receptor expression with RSV infection. Thus, targeting MMP-12 represents a potentially novel therapeutic strategy for the exacerbation of asthma.
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