ID 74742
Author
Pan, Hai-Yan 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
Keywords
influenza A virus
Toll-like receptor
proteinase-activated receptor-2
cardiomyocyte
Content Type
Journal Article
Description
Severe influenza sometimes causes myocarditis. We recently found that influenza A virus (IAV) infection induces various cellular factors, such as proinflammatory cytokines IL-6, IL-1β and TNF-α, matrix metalloproteinases (MMPs) and ectopic trypsin in mice hearts and in H9c2 cardiomyocytes. The induction of these cellular factors in turn promotes viral replication, myocardial inflammation and cellular damage through their intracellular signal transductions in cooperation with the IAV-induced Toll-like receptors (TLRs) and proteinase-activated receptor-2 (PAR-2) signallings, although the precise nature of these interactions remain obscure. By using specific inhibitors of TLRs and PAR-2 signalings and trypsin inhibitor aprotinin, we analyzed the role of TLR signaling and PAR-2 signaling in the IAV-induced pathological changes in cardiomyocytes. Inhibitors of TLR7/8-Myeloid Differentiation factor 88-nuclear factor-B signaling and aprotinin effectively suppressed IAV-induced upregulation of proinflammatory cytokines, MMPs, trypsinogen and viral replication. Inhibitor of TLR3-Toll/interleukin-1 receptor domain-containing adaptor inducing interferons-dependent signaling predominantly suppressed the upregulation of interferon-β, a key intracellular host immune response factor. In contrast to the suppressive effect of trypsin inhibitor aprotinin on IAV replication, PAR-2 inhibitor FSY-NH2, induced marginal upregulation of trypsinogen and subsequent stimulation of IAV replication.
Journal Title
The journal of medical investigation : JMI
ISSN
13431420
NCID
AA11166929
Volume
58
Issue
1-2
Start Page
19
End Page
28
Sort Key
19
Published Date
2011-02
Remark
The journal of medical investigation : http://medical.med.tokushima-u.ac.jp/jmi/index.html
EDB ID
FullText File
language
eng
departments
Institute of Advanced Medical Sciences