Onose Akira, Hashimoto Shu, Hayashi Shinichi, Maruoka Shuichiro, Kumasawa Fumio, Mizumura Kenji, Jibiki Itsuro, Matsumoto Ken, Gon Yasuhiro, Kobayashi Tomoko, Takahashi Noriaki, Shibata Yasuko, Abiko Yoshimitsu, Shibata Toshikatsu, Shimizu Kazufumi, Horie Takashi
Division of Respiratory Medicine, Department of Internal Medicine, Nihon University School of Medicine, Itabashi-ku, Tokyo, Japan.
Eur J Pharmacol. 2006 Jul 17;541(3):198-204. doi: 10.1016/j.ejphar.2006.03.073. Epub 2006 May 20.
Influenza is a major disease in humans. The reemergence of avian influenza A viruses has indicated that hyperinflammatory responses are closely related to the severity of disease. Influenza virus infection induces nuclear transcription factor kappaB (NF-kappaB) activation. NF-kappaB and NF-kappaB-dependent gene products promote lung inflammation and injury. Therefore, it is important to investigate the means to attenuate NF-kappaB activation. A20 is a cytoplasmic zinc finger protein that inhibits NF-kappaB activity, However, little is known about the role of A20 in influenza virus infection. Here, we have examined the role of A20 in influenza virus infection-induced NF-kappaB promoter activation in human bronchial epithelial cells. The results showed that (1) A20 protein and mRNA are inducible and expressed in the lung from mice and human bronchial epithelial cells upon influenza virus infection; (2) NF-kappaB promoter activation was induced in bronchial epithelial cells upon influenza virus infection; and (3) overexpression by transient transfection of A20 attenuated NF-kappaB promoter activation in bronchial epithelial cells. These results indicate that A20 may function as a negative regulator of NF-kappaB-mediated lung inflammation and injury upon influenza virus infection, thereby protecting the host against inflammatory response to influenza virus infection.
流感是人类的一种主要疾病。甲型禽流感病毒的再次出现表明，过度炎症反应与疾病的严重程度密切相关。流感病毒感染会诱导核转录因子κB（NF-κB）激活。NF-κB及依赖NF-κB的基因产物会促进肺部炎症和损伤。因此，研究减弱NF-κB激活的方法很重要。A20是一种抑制NF-κB活性的细胞质锌指蛋白，然而，关于A20在流感病毒感染中的作用知之甚少。在此，我们研究了A20在流感病毒感染诱导的人支气管上皮细胞NF-κB启动子激活中的作用。结果显示：（1）流感病毒感染后，小鼠肺部和人支气管上皮细胞中的A20蛋白和mRNA可被诱导并表达；（2）流感病毒感染后，支气管上皮细胞中NF-κB启动子被激活；（3）通过瞬时转染过表达A20可减弱支气管上皮细胞中NF-κB启动子的激活。这些结果表明，A20可能作为NF-κB介导的流感病毒感染后肺部炎症和损伤的负调节因子，从而保护宿主免受流感病毒感染引发的炎症反应。
