Role of protein kinase R in double-stranded RNA-induced expression of nitric oxide synthase in human astroglia

Corey J. Auch, Ramendra N. Saha, Faruk G. Sheikh, Xiaojuan Liu, Bertram Jacobs, Kalipada Pahan

Research output: Contribution to journalArticle

41 Scopus citations

Abstract

Environmental factor(s), such as viral infection, has been implicated as one of the triggering events leading to neuroinflammation in multiple sclerosis. This study underlines the importance of double-stranded RNA (dsRNA), the active component of a viral infection, in inducing the expression of inducible nitric oxide synthase (iNOS) in human astroglia. DsRNA in the form of synthetic polyinosinic-polycytidylic acid (poly IC) induced expression of iNOS and iNOS promoter-driven luciferase activity through activation of nuclear factor (NF)-κB and CCAAT/enhancer-binding proteinβ (C/EBPβ). In addition, we show that inhibitors of protein kinase R attenuated iNOS by suppressing the activation of NF-κB but not C/EBPβ. In contrast, knock down of p38 mitogen-activated protein kinase (MAPK) attenuated iNOS by suppressing the activation of C/EBPβ but not NF-κB. This study delineates a novel role of dsRNA in inducing the expression of iNOS through dsRNA-activated protein kinase (PKR)-mediated activation of NF-κB and p38-mediated activation of C/EBPβ in human astroglia that may participate in virus-induced neurological abnormalities.

Original languageEnglish (US)
Pages (from-to)223-228
Number of pages6
JournalFEBS Letters
Volume563
Issue number1-3
DOIs
StatePublished - Apr 9 2004

Keywords

  • CCAAT/enhancer-binding proteinβ
  • Double-stranded RNA
  • Human astroglia
  • Inducible nitric oxide synthase
  • Nuclear factor-κB

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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