Anti-inflammatory and antiviral effects of indirubin derivatives in influenza A (H5N1) virus infected primary human peripheral blood-derived macrophages and alveolar epithelial cells

Chris K.P. Mok, Sara S.R. Kang, Renee W.Y. Chan, Patrick Y K YUE, Nai Ki MAK, Leo L.M. Poon, Ricky N S WONG, J. S.Malik Peiris, Michael C.W. Chan*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

27 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)95-104
Number of pages10
JournalAntiviral Research
Volume106
Issue number1
DOIs
Publication statusPublished - Jun 2014

Scopus Subject Areas

  • Pharmacology
  • Virology

User-Defined Keywords

  • Indirubin
  • Influenza
  • IP-10
  • Macrophages
  • Pneumocytes

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