STAT1/IRF-1 signaling pathway mediates the injurious effect of interferon-gamma on oligodendrocyte progenitor cells
✍ Scribed by Yan Wang; Zhihua Ren; Duan Tao; Shilpa Tilwalli; Rajendra Goswami; Roumen Balabanov
- Publisher
- John Wiley and Sons
- Year
- 2010
- Tongue
- English
- Weight
- 917 KB
- Volume
- 58
- Category
- Article
- ISSN
- 0894-1491
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✦ Synopsis
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‐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.