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: Akira Onose, Shu Hashimoto, Shinichi Hayashi, Shuichiro Maruoka, Fumio Kumasawa, Kenji Mizumura, Itsuro Jibiki, Ken Matsumoto, Yasuhiro Gon, Tomoko Kobayashi, Noriaki Takahashi, Yasuko Shibata, Yoshimitsu Abiko, Toshikatsu Shibata, Kazufumi Shimizu, Takashi Horie
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 541 Issue 3 Pg. 198-204 (Jul 17 2006) ISSN: 0014-2999 [Print] Netherlands
• PMID: 16765340 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA-Binding Proteins
• Intracellular Signaling Peptides and Proteins
• NF-kappa B
• Nuclear Proteins
• Proteins
• RNA, Messenger
• TNFAIP3 protein, human
• Tumor Necrosis Factor alpha-Induced Protein 3
• Cysteine Endopeptidases
• Tnfaip3 protein, mouse

Topics

• Animals
• Blotting, Western
• Cell Line
• Cysteine Endopeptidases
• DNA-Binding Proteins
• Humans
• Immunoenzyme Techniques
• Influenza A virus (growth & development)
• Intracellular Signaling Peptides and Proteins
• Mice
• Mice, Inbred C57BL
• NF-kappa B (metabolism)
• Nuclear Proteins
• Proteins (genetics, pharmacology)
• RNA, Messenger (metabolism)
• Respiratory Mucosa (drug effects, metabolism, virology)
• Reverse Transcriptase Polymerase Chain Reaction
• Tumor Necrosis Factor alpha-Induced Protein 3