RGD Reference Report - Mechanisms of matrix metalloproteinase-9 upregulation and tissue destruction in various organs in influenza A virus infection. - Rat Genome Database

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Mechanisms of matrix metalloproteinase-9 upregulation and tissue destruction in various organs in influenza A virus infection.

Authors: Wang, S  Quang Le, T  Chida, J  Cisse, Y  Yano, M  Kido, H 
Citation: Wang S, etal., J Med Invest. 2010 Feb;57(1-2):26-34.
RGD ID: 5130855
Pubmed: PMID:20299740   (View Abstract at PubMed)

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-alpha) in various organs after intranasal infection of influenza A WSN virus. MMP-9 and TNF-alpha 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-alpha antibodies and by anti-oxidative reagents pyrrolidine dithiocarbamate and N-acetyl-L-cysteine, which inhibit activation of nuclear factor kappa B (NF-kappaB), as well as by nordihydroguaiaretic acid, which inhibits activation of activator protein 1 (AP-1). In addition, MMP-9 upregulation via TNF-alpha 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-kappaB- and/or AP-1-dependent mechanisms. Strategies that neutralize TNF-alpha as well as inhibitors of MAPK-NF-kappa 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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Human Influenza  ISOMmp9 (Mus musculus)5130855; 5130855protein:increased activity:lung more ...RGD 
Human Influenza  IEP 5130855protein:increased activity:lung more ...RGD 

Objects Annotated

Genes (Rattus norvegicus)
Mmp9  (matrix metallopeptidase 9)

Genes (Mus musculus)
Mmp9  (matrix metallopeptidase 9)

Genes (Homo sapiens)
MMP9  (matrix metallopeptidase 9)


Additional Information