Anti-inflammatory and antiviral effects of indirubin derivatives in influenza A (H5N1) virus infected primary human peripheral blood-derived macrophages and alveolar epithelial cells.
Human disease caused by highly pathogenic avian influenza A (HPAI) (H5N1) is associated with fulminant viral 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.
Centre of Influenza Research, School of Public Health, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region; The HKU-Pasteur Research Pole, School of Public Health, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region.
Chris K P
CK
Mok
Centre of Influenza Research, School of Public Health, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region.
Sara S R
SS
Kang
Centre of Influenza Research, School of Public Health, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region.
Renee W Y
RW
Chan
Department of Biology, Faculty of Science, Hong Kong Baptist University, Hong Kong Special Administrative Region.
Patrick Y K
PY
Yue
Department of Biology, Faculty of Science, Hong Kong Baptist University, Hong Kong Special Administrative Region.
Nai K
NK
Mak
Centre of Influenza Research, School of Public Health, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region.
Leo L M
LL
Poon
Department of Biology, Faculty of Science, Hong Kong Baptist University, Hong Kong Special Administrative Region.
Ricky N S
RN
Wong
Centre of Influenza Research, School of Public Health, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region; The HKU-Pasteur Research Pole, School of Public Health, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region.
J S Malik
JS
Peiris
Centre of Influenza Research, School of Public Health, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region. Electronic address: mchan@hku.hk.
Michael C W
MC
Chan
D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000998:Antiviral Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D016207:Cytokines / Q000037:antagonists & inhibitors; D004847:Epithelial Cells / Q000187:drug effects* / Q000821:virology; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D053124:Influenza A Virus, H5N1 Subtype / Q000187:drug effects* / Q000254:growth & development / Q000276:immunology*; D008264:Macrophages / Q000187:drug effects* / Q000821:virology; D014779:Virus Replication / Q000187:drug effects
D000893:Anti-Inflammatory Agents; D000998:Antiviral Agents; D016207:Cytokines; D007211:Indoles; C027185:indirubin
IP-10; Indirubin; Influenza; Macrophages; Pneumocytes