Central Role of Double-Stranded RNA-Activated Protein Kinase in Microbial Induction of Nitric Oxide Synthase
| Autor: | Sandy D. Der, Kohsaku Uetani, Carol A. de la Motte, Bryan R.G. Williams, Belinda Y. Lieberman, Serpil C. Erzurum, Maryam Zamanian-Daryoush |
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| Rok vydání: | 2000 |
| Předmět: |
viruses
Immunology Nitric Oxide Synthase Type II Bronchi Biology Mice eIF-2 Kinase parasitic diseases Gene expression Null cell Animals Humans Immunology and Allergy Protein kinase A Cells Cultured RNA Double-Stranded Mice Knockout NF-kappa B virus diseases Epithelial Cells respiratory system Phosphoproteins Protein kinase R Virology Cell biology DNA-Binding Proteins Enzyme Activation Mice Inbred C57BL Nitric oxide synthase RNA silencing Influenza A virus Enzyme Induction biology.protein RNA Viral Respiratory epithelium Nitric Oxide Synthase Signal transduction Interferon Regulatory Factor-1 |
| Zdroj: | The Journal of Immunology. 165:988-996 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.165.2.988 |
| Popis: | NO synthase 2 (NOS2) is induced in airway epithelium by influenza virus infection. NOS2 induction late in the course of viral infection may occur in response to IFN-γ, but early in infection gene expression may be induced by the viral replicative intermediate dsRNA through the dsRNA-activated protein kinase (PKR). Since PKR activates signaling pathways important in NOS2 gene induction, we determined whether PKR is a component in the signal transduction pathway leading to NOS2 gene expression after viral infection of airway epithelium. We show that NOS2 gene expression in human airway epithelial cells occurs in response to influenza A virus or synthetic dsRNA. Furthermore, dsRNA leads to rapid activation of PKR, followed by activation of signaling components including NF-κB and IFN regulatory factor 1. NOS2 expression is markedly diminished and IFN regulatory factor 1 and NF-κB activation are substantially impaired in PKR null cells. Strikingly, NOS2 induction in response to LPS is abolished in PKR null cells, confirming a central role for PKR in the general signaling pathway to NOS2. |
| Databáze: | OpenAIRE |
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