Protein kinase R, IkappaB kinase-beta and NF-kappaB are required for human rhinovirus induced pro-inflammatory cytokine production in bronchial epithelial cells.

Protein kinase R, IkappaB kinase-beta and NF-kappaB are required for human rhinovirus induced pro-inflammatory cytokine production in bronchial epithelial cells. Research Abstract Details 

Research Abstract Table of Contents

Jump to the:

Protein kinase R, IkappaB kinase-beta and NF-kappaB are required for human rhinovirus induced pro-inflammatory cytokine production in bronchial epithelial cells. Abstract Text:

Michael R Edwards,Christopher A Hewson,Vasile Laza-Stanca,Hoy-Tsun H Lau,Naofumi Mukaida,Marc B Hershenson,Sebastian L Johnston,

Rhinovirus infections cause the majority of acute exacerbations of airway diseases such as asthma and chronic obstructive pulmonary disease, with increased pro-inflammatory cytokine production by infected bronchial epithelial cells contributing to disease pathogenesis. Theses diseases are a huge cause of morbidity worldwide, and contribute a major economic burden to healthcare costs. Current steroid based treatments are only partially efficient at controlling virus induced inflammation, which remains an unmet therapeutic goal. Although NF-kappaB has been implicated, the precise mechanisms of rhinovirus induction of pro-inflammatory gene expression in bronchial epithelial cells are unclear. We hypothesised that rhinovirus replication and generation of dsRNA was an important process of pro-inflammatory cytokine induction. Using pharmalogical (2-aminopurine and a new small molecule inhibitor) and genetic inhibition of the dsRNA binding kinase protein kinase R, striking inhibition of dsRNA (polyrIC) and rhinovirus induced CCL5, CXCL8 and IL-6 protein was observed. Using confocal microscopy, rhinovirus induced protein kinase R phosphorylation co-located with NF-kappaB p65 nuclear translocation. Focusing on CXCL8, both rhinovirus infection and dsRNA treatment required IkappaB kinase-beta for induction of CXCL8. Analysis of cis-acting sites in the CXCL8 promoter revealed that both rhinovirus infection and dsRNA treatment upregulated CXCL8 promoter activation via NF-kappaB and NF-IL6 binding sites. Together, the results demonstrate the importance of dsRNA in induction of pro-inflammatory cytokines by rhinoviruses, and suggest that protein kinase R is involved in NF-kappaB mediated gene transcription of pro-inflammatory cytokines via IkappaB kinase-beta. These molecules regulating rhinovirus induction of inflammation represent therapeutic targets.

Protein kinase R, IkappaB kinase-beta and NF-kappaB are required for human rhinovirus induced pro-inflammatory cytokine production in bronchial epithelial cells. Publishing Authors By Initials

MR Edwards,CA Hewson,V Laza-Stanca,HT Lau,N Mukaida,MB Hershenson,SL Johnston,

For similar enzymes and coenzymes: enzymes: transferases: phosphotransferases: phosphotransferases (alcohol group acceptor): protein kinases: protein-serine-threonine kinases: eif-2 kinase research abstracts see: enzymes and coenzymes: enzymes: transferases: phosphotransferases: phosphotransferases (alcohol group acceptor): protein kinases: protein-serine-threonine kinases: eif-2 kinase research

PUBMED ID PMID:

MEDLINE DATE:

Protein kinase R, IkappaB kinase-beta and NF-kappaB are required for human rhinovirus induced pro-inflammatory cytokine production in bronchial epithelial cells. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Molecular immunology

VOLUME: 44

Page Numbers: 1587-97

Journal Abbreviation: Mol. Immunol.

ISSN: 0161-5890

DAY: 20

MONTH: 09

YEAR: 2006

Protein kinase R, IkappaB kinase-beta and NF-kappaB are required for human rhinovirus induced pro-inflammatory cytokine production in bronchial epithelial cells. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 7905289

Protein kinase R, IkappaB kinase-beta and NF-kappaB are required for human rhinovirus induced pro-inflammatory cytokine production in bronchial epithelial cells. Keywords Mesh Terms:

KEYWORDS: eIF-2 Kinase

MESH TERMS: metabolism

Chemical & Substance for Abstract: Protein kinase R, IkappaB kinase-beta and NF-kappaB are required for human rhinovirus induced pro-inflammatory cytokine production in bronchial epithelial cells. Information

Substance Name: eIF-2 Kinase

Registry Number: EC 2.7.1.37

Grant and Affiliation Information for Protein kinase R, IkappaB kinase-beta and NF-kappaB are required for human rhinovirus induced pro-inflammatory cytokine production in bronchial epithelial cells.

AFFILIATION: Department of Respiratory Medicine, National Heart Lung Institute and Wright Fleming Institute of Infection and Immunity, Imperial College London, Norfolk Place, London W2 1PG, UK. michael.edwards@ic.ac.uk

Country: England

AGENCY: United States NHLBI

GRANT: HL56399

ACRONYM: HL

MEDLINETA: Mol Immunol

REFSOURCE:

DATABASENAME:

ACCESSION NUMBER:

Number Hits: 0

Protein kinase R, IkappaB kinase-beta and NF-kappaB are required for human rhinovirus induced pro-inflammatory cytokine production in bronchial epithelial cells Related Publications

• Cancer cachexia - A clinical entity?
• Comparison of body protein metabolism during total parenteral nutrition using glucose or glucose and fat as the energy source.
• Cross-cultural differences in beliefs and practices that affect the language spoken to children: mothers with Indian and Western heritage.
• Deletion of Kv4.2 gene eliminates dendritic A-type K+ current and enhances induction of long-term potentiation in hippocampal CA1 pyramidal neurons.
• Dominant-subordinate relationships in hamsters: sex differences in reactions to familiar opponents.
• Foreign bodies in the air and food passages.
• Impact of comorbidities on the measurement of health in patients with ankle osteoarthritis.
• Mycobacterial bacilli are metabolically active during chronic tuberculosis in murine lungs: insights from genome-wide transcriptional profiling.
• Osteopathic manipulative treatment of a 27-year-old man after anterior cruciate ligament reconstruction.
• Possible four-electrode configurations for measuring cardiac tissue fiber rotation.
• Post-operative fatigue - a real phenomenon attributable to the metabolic effects of surgery on body nutritional stores.
• Preliminary investigation of breast tumor detection using cross-vivaldi antenna.
• Protein kinase R, IkappaB kinase-beta and NF-kappaB are required for human rhinovirus induced pro-inflammatory cytokine production in bronchial epithelial cells.
• Relationship Between Vitamin C Status and Respiratory Exchange Ratio During Submaximal Exercise in Healthy Adults: 2488: Board #35 June 2 8:00 AM - 9:30 AM.
• Relationships between growth and retention of dietary lipids in juvenile southern rock lobster Jasus edwardsii.
• Role of deficient type III interferon-lambda production in asthma exacerbations.
• State-dependent modulation of amygdala inputs by dopamine-induced enhancement of sodium currents in layer V entorhinal cortex.
• Synthesis of an advanced intermediate en route to the mitomycin natural products.
• Systematic reviews from the cochrane musculoskeletal group.
• The infant with respiratory stridor.
• The need to include BIPP reactions in routine consent.
• The rat epididymal transcriptome: comparison of segmental gene expression in the rat and mouse epididymides.
• The role of barium swallow in the management of the globus pharyngeus.
• The role of spermidine/spermine N1-acetyltransferase in determining response to chemotherapeutic agents in colorectal cancer cells.
• The role of the proteasomal ATPases and activator monoubiquitylation in regulating Gal4 binding to promoters.
• The thin child.
• Total hip arthroplasty with a cemented, polished, collared femoral stem and a cementless acetabular component. A follow-up study at a minimum of ten years.
• Vaccination with Venezuelan equine encephalitis replicons encoding cowpox virus structural proteins protects mice from intranasal cowpox virus challenge.
• Vitamin C Status is Directly Associated with Brachial Artery Distensibility Following Maximal Exercise in Adults: 1689: Board #179 May 30 2:00 PM - 3:30 PM.
• shRNAs targeting hepatitis C: effects of sequence and structural features, and comparision with siRNA.