Immunomodulatory role of focal adhesion kinase in human macrophages and pneumocytes during influenza A/H5N1 virus infection

Identification: Ng, Mandy Man Ting


Description

 

Immunomodulatory role of focal adhesion kinase in human macrophages and pneumocytes during influenza A/H5N1 virus infection
 
Mandy Man Ting Ng1, Michael Chi Wai Chan1, Kenrie Pui Yan Hui1
1School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong
      
Influenza A/H5N1 is a highly pathogenic influenza virus and poses a pandemic threat. Upon H5N1 virus infection, there is a hyperinduction of cytokines produced by macrophages and pneumocytes; both cell types are targets of H5N1 influenza virus infection. Dysregulation of cytokine induction is believed to contribute to the pathogenesis of H5N1 disease in humans. Cellular molecules of intracellular cascades have emerged as targets in novel influenza treatments. Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that resides at focal adhesions in cells. Previous studies have demonstrated that influenza virus binding to host cells are able to activate multiple intracellular pathways including the phosphatidylinositol-3-kinase (PI3K)-AKT signalling pathway which is linked to FAK. This study investigated the role of FAK during H5N1 influenza virus infection in human macrophages and human alveolar epithelial cells.
 
Using quantitative polymerase chain reaction, the mRNA levels of pro-inflammatory cytokines i.e. IFN-beta, TNF-alpha, IP-10, in human macrophages and pneumocytes infected with H5N1 influenza virus were significantly reduced by inhibition of FAK activity compared to vehicle-treated, virus-infected cells. In our previous publication, we showed by Western blot analysis that H5N1-infected primary cells strongly activated interferon regulatory factor 3 (IRF3) and p38 mitogen-activated protein kinase (p38); both are linked to the induction of proinflammatory cytokines and chemokines in virus-infected primary cells. Inhibition of FAK activity reduced the activation of IRF3 and p38 in H5N1-infected cells. Our results demonstrate immunomodulatory activities of FAK during H5N1 infection and support targeting FAK as a novel therapeutic option. Further studies of signalling molecules related to FAK will disclose more host-targeted options for future development to confront severe influenza disease.
 
 

 

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