Na Zhou, Siyi Che, Jiao Liu, Zhenghong Jiang, Luo Ren, Yin Liu, Enmei Liu, Jun Xie
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引用次数: 0
Abstract
Background: Andrographolide sulfonate (Andro-S), a traditional Chinese medicine, is commonly used to treat pediatric respiratory tract infections in China. However, its therapeutic effects in infections caused by respiratory syncytial virus (RSV) have not been reported. We thus aimed to investigate the therapeutic effects of Andro-S using a mouse model of RSV infection-induced airway inflammation.
Methods: Immunocompromised (cyclophosphamide-treated) BALB/c mice were intranasally infected with RSV and treated with intranasal or intraperitoneal Andro-S once daily for five consecutive days, starting on the day of infection. Histopathological changes in the lung were evaluated using hematoxylin and eosin staining. Total inflammatory cell counts and macrophage, lymphocyte, neutrophil, and eosinophil counts in the bronchoalveolar lavage fluid (BALF) were microscopically determined. Interferon-γ (IFN-γ) levels in the BALF were detected using enzyme-linked immunosorbent assay (ELISA). The messenger RNA levels of RSV nucleoprotein (N) and Toll-like receptors (TLRs) 1-9 in lung tissues were determined with quantitative real-time polymerase chain reaction (qRT-PCR). The protein levels of RSV N, RSV fusion protein (F), TLR2, TLR3, and TIR domain-containing adapter-inducing interferon-β (TRIF) were detected via Western blot analysis.
Results: RSV infection caused lung inflammation, manifesting as bronchiolitis, alveolitis, and perivascular inflammation; increased the number of inflammatory cells; and elevated IFN-γ levels in the BALF. Lung inflammation was positively correlated with pulmonary RSV N levels in infected mice. Intranasal Andro-S significantly downregulated RSV N, RSV F, TLR3, and TRIF protein expression in the lung and ameliorated lung inflammation in infected animals. However, intraperitoneal Andro-S showed no effects on lung inflammation caused by RSV infection.
Conclusions: Intranasal Andro-S inhibits RSV replication and ameliorates RSV infection-induced lung inflammation by downregulating TLR3 and TRIF. Therefore, intranasal administration may be a suitable drug delivery method for treating RSV infection.
期刊介绍:
The Journal of Thoracic Disease (JTD, J Thorac Dis, pISSN: 2072-1439; eISSN: 2077-6624) was founded in Dec 2009, and indexed in PubMed in Dec 2011 and Science Citation Index SCI in Feb 2013. It is published quarterly (Dec 2009- Dec 2011), bimonthly (Jan 2012 - Dec 2013), monthly (Jan. 2014-) and openly distributed worldwide. JTD received its impact factor of 2.365 for the year 2016. JTD publishes manuscripts that describe new findings and provide current, practical information on the diagnosis and treatment of conditions related to thoracic disease. All the submission and reviewing are conducted electronically so that rapid review is assured.