Analysis of gene expression in human bronchial epithelial cells upon influenza virus infection and regulation by p38 mitogen-activated protein kinase and c-Jun-N-terminal kinase

Division of Respiratory Disease, Department of Internal Medicine, School of Medicine, Nihon University, Tokyo, Japan.
Respirology (Impact Factor: 3.35). 04/2008; 13(2):203-14. DOI: 10.1111/j.1440-1843.2007.01204.x
Source: PubMed


Airway epithelial cells, which are the initial site of influenza virus (IV) infection, participate in the inflammatory process through the expression of various genes. In this process, mitogen-activated protein kinase (MAPK) may be associated with the expression of many genes, but its precise role remains unknown.
A comprehensive analysis was performed of gene expression in human bronchial epithelial cells upon IV infection, using an Affymetrix gene chip containing 12 000 genes. Regulation of gene expression by MAPK was also analysed.
A total of 5998 genes were detected. Upon IV infection, 165 genes were upregulated and 49 of these were interferon-stimulated genes. The functions of 129 genes, including 14 apoptosis-related genes and 6 antiviral genes, were well characterized; however, those of 36 genes were unknown. The expression of 29 genes was inhibited either by SB 203580, a specific inhibitor of p38 MAPK, or by CEP-11004, a specific inhibitor of the c-Jun-N-terminal kinase (JNK) cascade, and the percentage inhibition by SB 203580 correlated with that by CEP-11004, suggesting that p38 and JNK participate in a common downstream pathway involved in the regulation of gene expression. p38 MAPK- or JNK-dependent genes were functionally classified into diverse categories.
Although further studies are needed to obtain a more complete understanding of gene expression and the role of MAPK in gene expression, the present results are important in understanding the molecular mechanisms involved in the response of bronchial epithelial cells to IV infection.

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    • "This review highlighted the earlier work of Toth et al that identified 75 immune related genes (including 13 interferon related genes and 10 chemokine related genes) that were differentially expressed in C57BL/6J compared to BALB/cByJ mice in response to influenza H3N2 HK-X31 infection [35]. The review also identified increased expression of seven common genes in both H1N1/1918 and H3N2 HK-X31 infection of BALB/c mice, and 17 genes that showed increased expression in both human bronchial epithelial cell lines and mice infected with H3N2 (A/Udon/307/72 human bronchial epithelial cell, HK-X31 mice) [35], [90]-[92]. The review by Zhang et al proposed a list of around 100 candidate genes that may be related to susceptibility to influenza infection based on existing knowledge of the proteins involved in virus replication and the innate immune response [9]. "
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