Auch Corey J, Saha Ramendra N, Sheikh Faruk G, Liu Xiaojuan, Jacobs Bertram L, Pahan Kalipada
Department of Oral Biology, University of Nebraska Medical Center, Lincoln, NE 68583-0740, USA.
FEBS Lett. 2004 Apr 9;563(1-3):223-8. doi: 10.1016/S0014-5793(04)00302-3.
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)-kappaB and CCAAT/enhancer-binding proteinbeta (C/EBPbeta). In addition, we show that inhibitors of protein kinase R attenuated iNOS by suppressing the activation of NF-kappaB but not C/EBPbeta. In contrast, knock down of p38 mitogen-activated protein kinase (MAPK) attenuated iNOS by suppressing the activation of C/EBPbeta but not NF-kappaB. This study delineates a novel role of dsRNA in inducing the expression of iNOS through dsRNA-activated protein kinase (PKR)-mediated activation of NF-kappaB and p38-mediated activation of C/EBPbeta in human astroglia that may participate in virus-induced neurological abnormalities.
环境因素，如病毒感染，被认为是导致多发性硬化症神经炎症的触发事件之一。本研究强调了病毒感染的活性成分双链RNA（dsRNA）在诱导人星形胶质细胞中诱导型一氧化氮合酶（iNOS）表达方面的重要性。合成的聚肌苷酸-聚胞苷酸（poly IC）形式的dsRNA通过激活核因子（NF）-κB和CCAAT/增强子结合蛋白β（C/EBPβ）诱导iNOS的表达以及iNOS启动子驱动的荧光素酶活性。此外，我们表明蛋白激酶R抑制剂通过抑制NF-κB的激活而非C/EBPβ的激活来减弱iNOS。相反，敲低p38丝裂原活化蛋白激酶（MAPK）通过抑制C/EBPβ的激活而非NF-κB的激活来减弱iNOS。本研究描述了dsRNA在人星形胶质细胞中通过dsRNA激活的蛋白激酶（PKR）介导的NF-κB激活和p38介导的C/EBPβ激活来诱导iNOS表达的新作用，这可能参与病毒诱导的神经异常。
