Effects of inhibitors of Toll-like receptors, protease-activated receptor-2 signalings and trypsin on influenza A virus replication and upregulation of cellular factors in cardiomyocytes

• 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

抄録

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-κB 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. J. Med. Invest. 58: 19-28, February, 2011

収録刊行物

• The Journal of Medical Investigation

  The Journal of Medical Investigation 58 (1,2), 19-28, 2011

  国立大学法人　徳島大学医学部

キーワード

• influenza A virus
• Toll-like receptor
• proteinase-activated receptor-2
• cardiomyocyte

詳細情報

• CRID: 1390282679219624576
• NII論文ID: 130004465241
• NII論文ID: 120003596497
• NII書誌ID: AA11166929
• DOI: 10.2152/jmi.58.19
• COI: 1:STN:280:DC%2BC3M3jvVSitA%3D%3D
• ISSN: 13496867
• ISSN: 13431420
• PubMed: 21372483
• Web Site: http://repo.lib.tokushima-u.ac.jp/74742
• Web Site: http://www.jstage.jst.go.jp/article/jmi/58/1,2/58_1,2_19/_pdf
• 本文言語コード: en
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