期刊
FEBS LETTERS
卷 563, 期 1-3, 页码 223-228出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/S0014-5793(04)00302-3
关键词
double-stranded RNA; human astroglia; inducible nitric oxide synthase; nuclear factor-kappa B; CCAAT/enhancer-binding protein beta
资金
- NINDS NIH HHS [R01 NS039940-03, R01 NS039940, NS39940] Funding Source: Medline
Environmental factor(s), such as viral infection, has been implicated as one of the triggering events leading to neuro-inflammation 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. (C) 2004 Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies.
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