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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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
Externally publishedYes

Fingerprint

Encephalomyocarditis virus
diabetes
pathogenesis
src-Family Kinases
phosphotransferases (kinases)
macrophage activation
Macrophages
mice
Macrophage Activation
Nitric Oxide Synthase Type II
macrophages
tyrosine
Virus Activation
dosage
Inbred DBA Mouse
Interleukin-1
protein phosphorylation
Protein-Tyrosine Kinases
interleukin-1
cells

ASJC Scopus subject areas

  • Immunology

Cite this

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

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

In: Journal of Virology, Vol. 75, No. 4, 2001, p. 1949-1957.

Research output: Contribution to journalArticle

Choi, KS, Jun, HS, Kim, HN, Park, HJ, Eom, YW, Noh, HL, Kwon, H, Kim, HM & Yoon, JW 2001, 'Role of Hck in the pathogenesis of encephalomyocarditis virus-induced diabetes in mice', Journal of Virology, vol. 75, no. 4, pp. 1949-1957. https://doi.org/10.1128/JVI.75.4.1949-1957.2001
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. / Role of Hck in the pathogenesis of encephalomyocarditis virus-induced diabetes in mice. In: Journal of Virology. 2001 ; Vol. 75, No. 4. pp. 1949-1957.
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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.",
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AU - Kwon, H.

AU - Kim, H. M.

AU - Yoon, J. W.

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