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Cited by 100interferon and immune responsesImmune Response and InflammationNF-κB Signaling Pathways

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

Uetani, Kohsaku, Der, Sandy D, Zamanian-Daryoush, Maryam, de la Motte, Carol, Lieberman, Belinda Y, Williams, Bryan R G, Erzurum, Serpil C·2000·The Journal of Immunology
DOI 10.4049/jimmunol.165.2.988
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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.

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Authors
Uetani, K., Der, S. D., Zamanian-Daryoush, M., de la Motte, C., Lieberman, B. Y., Williams, B. R. G., & Erzurum, S. C.
Affiliations
  • Cleveland Clinic Lerner College of Medicine (US)
  • Cleveland Clinic Research (US)
  • Department of Immunology, Lerner Research Institute , Cleveland, OH 44195
  • Department of Microbiology, Cleveland Clinic Foundation, Lerner Research Institute , Cleveland, OH 44195
ORCID
Venue
The Journal of Immunology
Publisher
Oxford University Press (OUP)
Published
2000-07
Volume
165
Issue
2
Pages
988-996
ISSN
  • 0022-1767 (ISSN-L)
  • 1550-6606
DOI
10.4049/jimmunol.165.2.988
OpenAlex
W2098000889
Cited by
100
References
47
Citations by year
2022: 2 · 2021: 1 · 2020: 4 · 2019: 1 · 2018: 2 · 2016: 3 · 2015: 2 · 2014: 3 · 2013: 3 · 2012: 5
FWCI
3.42
Type
journal article
Language
en
Open access
closed
Licence
academic.oup.com/pages/standard-publication-reuse-rights (vor)
Locations
  • The Journal of Immunology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Genentech
  • National Heart, Lung, and Blood Institute (HL-60917)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
Keywords
double-stranded RNA-dependent protein kinase, PKR, nitric oxide synthase 2, influenza A virus, airway epithelial cells, double-stranded RNA, NF-κB, IRF1, interferon-gamma, lipopolysaccharide, viral infection, innate immunity
MeSH terms
Animals, Bronchi, Cells, Cultured, DNA-Binding Proteins, Enzyme Activation, Enzyme Induction, Epithelial Cells, Humans, Mice, Inbred C57BL, Influenza A virus, Phosphoproteins, RNA, Double-Stranded, RNA, Viral, NF-kappa B, Mice, Knockout, Nitric Oxide Synthase, eIF-2 Kinase, Interferon Regulatory Factor-1, Mice, Nitric Oxide Synthase Type II

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