The scope and activation mechanisms of chemokine gene expression in primary astrocytes following infection with Theiler's virus

Jo Ann P. Palma, Byung S. Kim*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

Abstract

Intracerebral infection with Theiler's virus induces a demyelinating disease that resembles human MS. In order to delineate the early events in virus-induced inflammatory disease, we have analyzed chemokine gene activation following Theiler's murine encephalomyelitis virus (TMEV) infection. Infection of primary astrocyte cultures results in activation of various chemokine genes (GRO-1, MCP-1, MCP-5, MIP-1α, MIP-1β, MIP-2, RANTES, IP-10 and MCP-3) that are important in the initiation of an inflammatory response. As early as 1-3 h after TMEV infection, chemokine gene expression is strongly activated. In addition, proinflammatory cytokines do not interfere with TMEV-induced chemokine gene expression and some cytokines may function synergistically for virus-induced upregulation of chemokine gene expression. Chemokine gene activation by TMEV appears to be largely independent of the IFNαβ pathway and partly dependent on dsRNA-dependent protein kinase (PKR) and MAP kinase pathways. However, TMEV-induced chemokine gene expression is completely dependent on the NFκB pathway. These results strongly suggest that the expression of select chemokine genes upon TMEV infection is activated via the NFκB pathway, similar to that of proinflammatory cytokine genes, and these cellular gene products appear to synergistically promote inflammatory responses in the CNS.

Original languageEnglish (US)
Pages (from-to)121-129
Number of pages9
JournalJournal of Neuroimmunology
Volume149
Issue number1-2
DOIs
StatePublished - Apr 2004

Keywords

  • Astrocytes
  • BBB
  • Blood-brain barrier
  • CNS
  • Chemokines
  • Double-stranded RNA
  • Innate immunity
  • PKR
  • TMEV
  • Theiler's murine encephalomyelitis virus
  • Viral inflammation
  • dsRNA
  • dsRNA-dependent protein kinase

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Neurology
  • Clinical Neurology

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