STAT1/IRF-1 signaling pathway mediates the injurious effect of interferon-gamma on oligodendrocyte progenitor cells

Yan Wang, Zhihua Ren, Duan Tao, Shilpa Tilwalli, Rajendra Goswami, Roumen Balabanov*

*Corresponding author for this work

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

Interferon-gamma (IFN-γ) is a pleiotropic cytokine that is critically involved in the pathogenesis of inflammatory demyelinating diseases. There is strong evidence that IFN-γ can function as a distinct and independent injurious factor to oligodendrocyte progenitor cells (OPCs). The intracellular signaling pathways leading to OPC death, however, remain poorly understood. In this study, we examined IFN-γ signaling in OPCs in relation to cell death in vitro. Using expression knock-down and forced overexpression methods, we directly demonstrated the role of signal transducer and transcription activator 1 (STAT1) and interferon-regulated factor 1 (IRF-1) in IFN-γ- induced OPC death. In addition, our study identified two proapoptotic genes, caspase 1 and double-stranded RNA-dependent protein kinase (PKR), whose expression was upregulated by IFN-g and transcriptionally controlled by IRF-1. The conclusion of this study is that STAT1 and IRF-1 function as components of the signaling pathway that mediates IFN-γ-induced OPC death.

Original languageEnglish (US)
Pages (from-to)195-208
Number of pages14
JournalGlia
Volume58
Issue number2
DOIs
StatePublished - 2010

Keywords

  • Cell signaling
  • IRF-1
  • Interferon-gamma
  • Oligodendrocyte progenitor cells
  • STAT1

ASJC Scopus subject areas

  • Neurology
  • Cellular and Molecular Neuroscience

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