期刊
ANTIVIRAL RESEARCH
卷 106, 期 -, 页码 95-104出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.antiviral.2014.03.019
关键词
Influenza; Indirubin; Macrophages; Pneumocytes; IP-10
资金
- Hong Kong SAR Government [11100972]
- National Institutes of Health (NIAID) [HHSN266200700005C]
- Area of Excellence Scheme of the University Grants Committee, Hong Kong SAR Government [AoE/M-12/06]
- Research Fund for Control of Infectious Disease, Food and Health Bureau
Human disease caused by highly pathogenic avian influenza A (HPAI) (H5N1) is associated with fulminant vital pneumonia and mortality rates in excess of 60%. Acute respiratory syndrome (ARDS) has been found to be the most severe form of acute lung injury caused by H5N1 virus infection while cytokine dysregulation and viral replication are thought to contribute to its pathogenesis. In this study, the antiviral and anti-inflammatory effects of two indirubin derivatives: indirubin-3'-oxime (IM) and E804 on primary human peripherial blood-derived macrophages and type-I like pneumocytes (human alveolar epithelial cells) during influenza A (H5N1) virus infection were investigated. We found that both of the indirubin derivatives strongly suppress the pro-inflammatory cytokines including IP-10 (CXCL10), one of the key factors which contribute to the lung inflammation during H5N1 virus infection. In addition, we also demonstrated that the indirubin derivative delays the virus replication in the primary cell culture models. Our results showed that indirubin derivatives have a potential to be used as an adjunct to antiviral therapy for the treatment of severe human H5N1 disease. (C) 2014 Elsevier B.V. All rights reserved.
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