DOI: 10.4049/jimmunol.165.2.988. Central Role of Double-Stranded RNA-Activated Protein Kinase in Microbial Induction of Nitric Oxide Synthase

Central Role of Double-Stranded RNA-Activated Protein Kinase in Microbial Induction of Nitric Oxide Synthase

10.4049/jimmunol.165.2.988

Crossref journal-article

Oxford University Press (OUP)

The Journal of Immunology (286)

Abstract

Abstract 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.

Bibliography

Uetani, K., Der, S. D., Zamanian-Daryoush, M., de la Motte, C., Lieberman, B. Y., Williams, B. R. G., & Erzurum, S. C. (2000). Central Role of Double-Stranded RNA-Activated Protein Kinase in Microbial Induction of Nitric Oxide Synthase. The Journal of Immunology, 165(2), 988â996.

Authors 7

Kohsaku Uetani (first)
Sandy D Der (additional)
Maryam Zamanian-Daryoush (additional)
Carol de la Motte (additional)
Belinda Y Lieberman (additional)
Bryan R G Williams (additional)
Serpil C Erzurum (additional)

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Dates

Type	When
Created	11 years, 4 months ago (April 21, 2014, 11:02 p.m.)
Deposited	5 months ago (March 31, 2025, 4:43 a.m.)
Indexed	3 months ago (June 2, 2025, 8:34 p.m.)
Issued	25 years, 2 months ago (July 1, 2000)
Published	25 years, 2 months ago (July 1, 2000)
Published Online	25 years, 1 month ago (July 15, 2000)
Published Print	25 years, 1 month ago (July 15, 2000)

Funders 0

None

BibTeX

@article{Uetani_2000, title={Central Role of Double-Stranded RNA-Activated Protein Kinase in Microbial Induction of Nitric Oxide Synthase}, volume={165}, ISSN={1550-6606}, url={http://dx.doi.org/10.4049/jimmunol.165.2.988}, DOI={10.4049/jimmunol.165.2.988}, number={2}, journal={The Journal of Immunology}, publisher={Oxford University Press (OUP)}, author={Uetani, Kohsaku and Der, Sandy D and Zamanian-Daryoush, Maryam and de la Motte, Carol and Lieberman, Belinda Y and Williams, Bryan R G and Erzurum, Serpil C}, year={2000}, month=jul, pages={988–996} }

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  "abstract": "<jats:title>Abstract</jats:title>\n               <jats:p>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-\u03b3, 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-\u03baB and IFN regulatory factor 1. NOS2 expression is markedly diminished and IFN regulatory factor 1 and NF-\u03baB 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.</jats:p>",
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