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

FEBS Letters

Auch, Corey J³  Sheikh, Faruk G¹  Jacobs, Bertram L²  Saha, Ramendra N³  Pahan, Kalipada³  Liu, Xiaojuan³ 

[1] Division of Therapeutic Protein, Food and Drug Administration, Bethesda, MD 20892, USA;Department of Microbiology, Arizona State University, Tempe, AZ 85287, USA;Department of Oral Biology, University of Nebraska Medical Center, 40 and Holdrege, Lincoln, NE 68583-0740, USA

关键词: Double-stranded RNA;    Human astroglia;    Inducible nitric oxide synthase;    Nuclear factor-κB;    CCAAT/enhancer-binding proteinβ;   

DOI  :  10.1016/S0014-5793(04)00302-3

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown