Hayashi Shinichi, Jibiki Itsuro, Asai Yasukiyo, Gon Yasuhiro, Kobayashi Tomoko, Ichiwata Toshio, Shimizu Kazufumi, Hashimoto Shu
Division of Respiratory Disease, Department of Internal Medicine, School of Medicine, Nihon University, Tokyo, Japan.
Respirology. 2008 Mar;13(2):203-14. doi: 10.1111/j.1440-1843.2007.01204.x.
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.
气道上皮细胞是流感病毒（IV）感染的初始部位，通过多种基因的表达参与炎症过程。在此过程中，丝裂原活化蛋白激酶（MAPK）可能与许多基因的表达相关，但其确切作用尚不清楚。
使用包含12000个基因的Affymetrix基因芯片，对IV感染后人支气管上皮细胞中的基因表达进行了全面分析。还分析了MAPK对基因表达的调控。
共检测到5998个基因。IV感染后，165个基因上调，其中49个是干扰素刺激基因。129个基因的功能已明确，包括14个凋亡相关基因和6个抗病毒基因；然而，36个基因的功能尚不清楚。29个基因的表达受到p38 MAPK的特异性抑制剂SB 203580或c-Jun-N-末端激酶（JNK）级联的特异性抑制剂CEP-11004的抑制，且SB 203580的抑制百分比与CEP-11004的抑制百分比相关，表明p38和JNK参与了调控基因表达的共同下游途径。p38 MAPK或JNK依赖性基因在功能上分为不同类别。
尽管需要进一步研究以更全面地了解基因表达以及MAPK在基因表达中的作用，但目前的结果对于理解支气管上皮细胞对IV感染反应的分子机制具有重要意义。
