ID 84287
Author
Wang, Siye Division of Enzyme Chemistry, Institute for Enzyme Research, the University of Tokushima
Le, Trong Quang Division of Enzyme Chemistry, Institute for Enzyme Research, the University of Tokushima
Chida, Junji Division of Enzyme Chemistry, Institute for Enzyme Research, the University of Tokushima Tokushima University Educator and Researcher Directory KAKEN Search Researchers
Cisse, Youssouf Division of Enzyme Chemistry, Institute for Enzyme Research, the University of Tokushima
Yano, Mihiro Division of Enzyme Chemistry, Institute for Enzyme Research, the University of Tokushima
Kido, Hiroshi Division of Enzyme Chemistry, Institute for Enzyme Research, the University of Tokushima Tokushima University Educator and Researcher Directory KAKEN Search Researchers
Content Type
Journal Article
Description
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-χB), 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 signalregulated
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-χB- and/or AP-1-dependent mechanisms. Strategies that neutralize
TNF-α as well as inhibitors of MAPK-NF-χB- and/or AP-1-dependent pathways
may be useful for suppressing the MMP-9 effect and thus preventing multiple organ failure
in severe influenza.
Journal Title
The journal of medical investigation : JMI
ISSN
13431420
NCID
AA11166929
Volume
57
Issue
1-2
Start Page
26
End Page
34
Sort Key
26
Published Date
2010-02
Remark
The journal of medical investigation : http://medical.med.tokushima-u.ac.jp/jmi/index.html
FullText File
language
eng
departments
Institute of Advanced Medical Sciences