Role of Hck in the pathogenesis of encephalomyocarditis virus-induced diabetes in mice

K. S. Choi, H. S. Jun, H. N. Kim, H. J. Park, Y. W. Eom, H. L. Noh, H. Kwon, H. M. Kim, J. W. Yoon

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13 Scopus citations

Abstract

Soluble mediators such as interleukin-1β, tumor necrosis factor alpha (TNF-α), and inducible nitric oxide synthase (iNOS) produced from activated macrophages play an important role in the destruction of pancreatic β cells in mice infected with a low dose of the D variant of encephalomyocarditis (EMC-D) virus. The tyrosine kinase signaling pathway was shown to be involved in EMC-D virus-induced activation of macrophages. This investigation was initiated to determine whether the Src family of kinases plays a role in the activation of macrophages, subsequently resulting in the destruction of β cells, in mice infected with a low dose of EMC-D virus. We examined the activation of p59/p56Hck, p55Fgr, and p56/p53Lyn in macrophages from DBA/2 mice infected with the virus. We found that p59/p56Hck showed a marked increase in both autophosphorylation and kinase activity at 48 h after infection, whereas p55Fgr and p56/p53Lyn did not. The p59/p56Hck activity was closely correlated with the tyrosine phosphorylation level of Vav. Treatment of EMC-D virus-infected mice with the Src kinase inhibitor, PP2, resulted in the inhibition of p59/p56Hck activity and almost complete inhibition of the production of TNF-α and iNOS in macrophages and the subsequent prevention of diabetes in mice. On the basis of these observations, we conclude that the Src kinase, p59/p56Hck, plays an important role in the activation of macrophages and the subsequent production of TNF-α and nitric oxide, leading to the destruction of pancreatic β cells, which results in the development of diabetes in mice infected with a low dose of EMC-D virus.

Original languageEnglish (US)
Pages (from-to)1949-1957
Number of pages9
JournalJournal of virology
Volume75
Issue number4
DOIs
StatePublished - 2001

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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    Choi, K. S., Jun, H. S., Kim, H. N., Park, H. J., Eom, Y. W., Noh, H. L., Kwon, H., Kim, H. M., & Yoon, J. W. (2001). Role of Hck in the pathogenesis of encephalomyocarditis virus-induced diabetes in mice. Journal of virology, 75(4), 1949-1957. https://doi.org/10.1128/JVI.75.4.1949-1957.2001