An inhibitory effect of A20 on NF-κB activation in airway epithelium upon influenza virus infection

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-κB) activation. NF-κB and NF-κB-dependent gene products promote lung inflammation and injury. Therefore, it is important to investigate the means to attenuate NF-κB activation. A20 is a cytoplasmic zinc finger protein that inhibits NF-κB 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-κB 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-κB promoter activation was induced in bronchial epithelial cells upon influenza virus infection; and (3) overexpression by transient transfection of A20 attenuated NF-κB promoter activation in bronchial epithelial cells. These results indicate that A20 may function as a negative regulator of NF-κB-mediated lung inflammation and injury upon influenza virus infection, thereby protecting the host against inflammatory response to influenza virus infection.