HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Uetani, K. Articles by Erzurum, S. C. Search for Related Content PubMed PubMed Citation Articles by Uetani, K. Articles by Erzurum, S. C.

Central Role of Double-Stranded RNA-Activated Protein Kinase in Microbial Induction of Nitric Oxide Synthase¹

Kohsaku Uetani^*,, Sandy D. Der, Maryam Zamanian-Daryoush, Carol de la Motte, Belinda Y. Lieberman^§, Bryan R. G. Williams and Serpil C. Erzurum^2,*,

Departments of ^* Pulmonary and Critical Care Medicine, Cancer Biology, Immunology, and ^§ Microbiology, Cleveland Clinic Foundation, Lerner Research Institute, Cleveland, OH 44195

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-, 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-B and IFN regulatory factor 1. NOS2 expression is markedly diminished and IFN regulatory factor 1 and NF-B 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.

This article has been cited by other articles:

				M. Cabanski, M. Steinmuller, L. M. Marsh, E. Surdziel, W. Seeger, and J. Lohmeyer PKR Regulates TLR2/TLR4-Dependent Signaling in Murine Alveolar Macrophages Am. J. Respir. Cell Mol. Biol., January 1, 2008; 38(1): 26 - 31. [Abstract] [Full Text] [PDF]

				D. Proud, S. P. Sanders, and S. Wiehler Human Rhinovirus Infection Induces Airway Epithelial Cell Production of Human {beta}-Defensin 2 Both In Vitro and In Vivo J. Immunol., April 1, 2004; 172(7): 4637 - 4645. [Abstract] [Full Text] [PDF]

				T. R. Meusel and F. Imani Viral Induction of Inflammatory Cytokines in Human Epithelial Cells Follows a p38 Mitogen-Activated Protein Kinase-Dependent but NF-{kappa}B-Independent Pathway J. Immunol., October 1, 2003; 171(7): 3768 - 3774. [Abstract] [Full Text] [PDF]

				W. Xu, S. A. A. Comhair, S. Zheng, S. C. Chu, J. Marks-Konczalik, J. Moss, S. J. Haque, and S. C. Erzurum STAT-1 and c-Fos interaction in nitric oxide synthase-2 gene activation Am J Physiol Lung Cell Mol Physiol, July 1, 2003; 285(1): L137 - L148. [Abstract] [Full Text] [PDF]

				J. E. Gern, D. A. French, K. A. Grindle, R. A. Brockman-Schneider, S.-I. Konno, and W. W. Busse Double-Stranded RNA Induces the Synthesis of Specific Chemokines by Bronchial Epithelial Cells Am. J. Respir. Cell Mol. Biol., June 1, 2003; 28(6): 731 - 737. [Abstract] [Full Text] [PDF]

				T. R. Meusel, K. E. Kehoe, and F. Imani Protein Kinase R Regulates Double-Stranded RNA Induction of TNF-{alpha} But Not IL-1{beta} mRNA in Human Epithelial Cells J. Immunol., June 15, 2002; 168(12): 6429 - 6435. [Abstract] [Full Text] [PDF]

				D. Liu, A. K. Cardozo, M. I. Darville, and D. L. Eizirik Double-Stranded RNA Cooperates with Interferon-{gamma} and IL-1{beta} to Induce Both Chemokine Expression and Nuclear Factor-{kappa}B-Dependent Apoptosis in Pancreatic {beta}-Cells: Potential Mechanisms for Viral-Induced Insulitis and {beta}-Cell Death in Type 1 Diabetes Mellitus Endocrinology, April 1, 2002; 143(4): 1225 - 1234. [Abstract] [Full Text] [PDF]

				T. Kawai, O. Takeuchi, T. Fujita, J.-i. Inoue, P. F. Muhlradt, S. Sato, K. Hoshino, and S. Akira Lipopolysaccharide Stimulates the MyD88-Independent Pathway and Results in Activation of IFN-Regulatory Factor 3 and the Expression of a Subset of Lipopolysaccharide-Inducible Genes J. Immunol., November 15, 2001; 167(10): 5887 - 5894. [Abstract] [Full Text] [PDF]

				I. Davis and S. Matalon Reactive Species in Viral Pneumonitis: Lessons From Animal Models Physiology, August 1, 2001; 16(4): 185 - 190. [Abstract] [Full Text] [PDF]

				M. J. de Veer, M. Holko, M. Frevel, E. Walker, S. Der, J. M. Paranjape, R. H. Silverman, and B. R. G. Williams Functional classification of interferon-stimulated genes identified using microarrays J. Leukoc. Biol., June 1, 2001; 69(6): 912 - 920. [Abstract] [Full Text] [PDF]

				D. Liu, M. Darville, and D. L. Eizirik Double-Stranded Ribonucleic Acid (RNA) Induces {beta}-Cell Fas Messenger RNA Expression and Increases Cytokine-Induced {beta}-Cell Apoptosis Endocrinology, June 1, 2001; 142(6): 2593 - 2599. [Abstract] [Full Text] [PDF]

				R. A. Dweik, S. A. A. Comhair, B. Gaston, F. B. J. M. Thunnissen, C. Farver, M. J. Thomassen, M. Kavuru, J. Hammel, H. M. Abu-Soud, and S. C. Erzurum NO chemical events in the human airway during the immediate and late antigen-induced asthmatic response PNAS, February 15, 2001; (2001) 51629498. [Abstract] [Full Text]

				R. A. Dweik, S. A. A. Comhair, B. Gaston, F. B. J. M. Thunnissen, C. Farver, M. J. Thomassen, M. Kavuru, J. Hammel, H. M. Abu-Soud, and S. C. Erzurum NO chemical events in the human airway during the immediate and late antigen-induced asthmatic response PNAS, February 27, 2001; 98(5): 2622 - 2627. [Abstract] [Full Text] [PDF]