title: An inhibitory effect of A20 on NF-kappaB activation in airway epithelium upon influenza virus infection.
abstract: 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.
authors.affiliation: Division of Respiratory Medicine, Department of Internal Medicine, Nihon University School of Medicine, Itabashi-ku, Tokyo, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Onose
authors.forename: Shu
authors.initials: S
authors.lastname: Hashimoto
authors.forename: Shinichi
authors.initials: S
authors.lastname: Hayashi
authors.forename: Shuichiro
authors.initials: S
authors.lastname: Maruoka
authors.forename: Fumio
authors.initials: F
authors.lastname: Kumasawa
authors.forename: Kenji
authors.initials: K
authors.lastname: Mizumura
authors.forename: Itsuro
authors.initials: I
authors.lastname: Jibiki
authors.forename: Ken
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Gon
authors.forename: Tomoko
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Noriaki
authors.initials: N
authors.lastname: Takahashi
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Shibata
authors.forename: Yoshimitsu
authors.initials: Y
authors.lastname: Abiko
authors.forename: Toshikatsu
authors.initials: T
authors.lastname: Shibata
authors.forename: Kazufumi
authors.initials: K
authors.lastname: Shimizu
authors.forename: Takashi
authors.initials: T
authors.lastname: Horie
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D003546:Cysteine Endopeptidases; D004268:DNA-Binding Proteins; D006801:Humans; D007124:Immunoenzyme Techniques; D009980:Influenza A virus / Q000254:growth & development*; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism*; D009687:Nuclear Proteins; D011506:Proteins / Q000235:genetics / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D020545:Respiratory Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000821:virology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3
chemical_list: D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D016328:NF-kappa B; D009687:Nuclear Proteins; D011506:Proteins; D012333:RNA, Messenger; C076529:TNFAIP3 protein, human; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; D003546:Cysteine Endopeptidases; C513261:Tnfaip3 protein, mouse