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STAT1/IRF‐1 signaling pathway mediates the injurious effect of interferon‐gamma on oligodendrocyte progenitor cells
Author(s) -
Wang Yan,
Ren Zhihua,
Tao Duan,
Tilwalli Shilpa,
Goswami Rajendra,
Balabanov Roumen
Publication year - 2009
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.20912
Subject(s) - biology , stat protein , microbiology and biotechnology , stat1 , signal transduction , interferon gamma , stat3 , irf1 , interferon regulatory factors , transcription factor , interferon , cytokine , oligodendrocyte , programmed cell death , progenitor cell , immunology , cancer research , apoptosis , stem cell , neuroscience , central nervous system , gene , myelin , genetics
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‐γ 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. © 2009 Wiley‐Liss, Inc.