Mechanisms of matrix metalloproteinase-9 upregulation and tissue destruction in various organs in influenza A virus infection
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- Wang Siye
- Division of Enzyme Chemistry, Institute for Enzyme Research, the University of Tokushima
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- Quang Le Trong
- Division of Enzyme Chemistry, Institute for Enzyme Research, the University of Tokushima
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- Chida Junji
- Division of Enzyme Chemistry, Institute for Enzyme Research, the University of Tokushima
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- Cisse Youssouf
- Division of Enzyme Chemistry, Institute for Enzyme Research, the University of Tokushima
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- Yano Mihiro
- Division of Enzyme Chemistry, Institute for Enzyme Research, the University of Tokushima
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- Kido Hiroshi
- Division of Enzyme Chemistry, Institute for Enzyme Research, the University of Tokushima
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Severe influenza is characterized clinicopathologically by multiple organ failure, although the relationship amongst virus and host factors that influence this morbid outcome and the underlying mechanisms of action remain unclear. The present study identified marked upregulation of matrix metalloproteinase (MMP)-9 and pro-inflammatory cytokine tumor necrosis factor alpha (TNF-α) in various organs after intranasal infection of influenza A WSN virus. MMP-9 and TNF-α were upregulated in the lung, the site of initial infection, as well as in the brain and heart. The infection-induced MMP-9 upregulation was inhibited by anti-TNF-α antibodies and by anti-oxidative reagents pyrrolidine dithiocarbamate and N-acetyl-L-cysteine, which inhibit activation of nuclear factor kappa B (NF-κB), as well as by nordihydroguaiaretic acid, which inhibits activation of activator protein 1 (AP-1). In addition, MMP-9 upregulation via TNF-α was also suppressed by inhibitors of mitogen-activated protein kinases (MAPKs), such as extracellular signal-regulated kinase 1/2 and p38, and partly by a c-Jun N-terminal kinase inhibitor. These results indicated that the influenza-induced MMP-9 upregulation in various organs is mediated through MAPK-NF-κB- and/or AP-1-dependent mechanisms. Strategies that neutralize TNF-α as well as inhibitors of MAPK-NF-κ B- and/or AP-1-dependent pathways may be useful for suppressing the MMP-9 effect and thus preventing multiple organ failure in severe influenza. J. Med. Invest. 57: 26-34, February, 2010
収録刊行物
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- The Journal of Medical Investigation
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The Journal of Medical Investigation 57 (1,2), 26-34, 2010
国立大学法人 徳島大学医学部
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詳細情報 詳細情報について
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- CRID
- 1390282679220181120
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- NII論文ID
- 130004465198
- 80020865948
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- NII書誌ID
- AA11166929
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- ISSN
- 13496867
- 13431420
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- IRDB
- Crossref
- CiNii Articles
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