Respiratory syncytial virus up-regulates TLR4 and sensitizes airway epithelial cells to endotoxin

Martha M Monick; Timur O Yarovinsky; Linda S Powers; Noah S Butler; A Brent Carter; Gunnar Gudmundsson; Gary W Hunninghake

doi:10.1074/jbc.M308093200

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Respiratory syncytial virus up-regulates TLR4 and sensitizes airway epithelial cells to endotoxin

Journal article

Open access

Peer reviewed

Respiratory syncytial virus up-regulates TLR4 and sensitizes airway epithelial cells to endotoxin

Martha M Monick, Timur O Yarovinsky, Linda S Powers, Noah S Butler, A Brent Carter, Gunnar Gudmundsson and Gary W Hunninghake

The Journal of biological chemistry, Vol.278(52), pp.53035-53044

12/26/2003

DOI: 10.1074/jbc.M308093200

PMID: 14565959

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Abstract

Airway epithelial cells are unresponsive to endotoxin (lipopolysaccharide (LPS)) exposure under normal conditions. This study demonstrates that respiratory syncytial virus (RSV) infection results in increased sensitivity to this environmental exposure. Infection with RSV results in increased expression of Toll-like receptor (TLR) 4 mRNA, protein, and increased TLR4 membrane localization. This permits significantly enhanced LPS binding to the epithelial monolayer that is blocked by disruption of the Golgi. The increased TLR4 results in an LPS-induced inflammatory response as demonstrated by increased mitogen-activated protein (MAP) kinase activity, IL-8 production, and tumor necrosis factor alpha production. RSV infection also allowed for tumor necrosis factor alpha production subsequent to TLR4 cross-linking with an immobilized antibody. These data suggest that RSV infection sensitizes airway epithelium to a subsequent environmental exposure (LPS) by altered expression and membrane localization of TLR4. The increased interaction between airway epithelial cells and LPS has the potential to profoundly alter airway inflammation.

Tumor Necrosis Factor-alpha - metabolism

Up-Regulation

Epithelial Cells - metabolism

Toll-Like Receptor 4

Cross-Linking Reagents - pharmacology

Humans

Membrane Glycoproteins - biosynthesis

Membrane Glycoproteins - chemistry

Lipopolysaccharides - metabolism

Monocytes - metabolism

RNA, Messenger - metabolism

MAP Kinase Signaling System

Dose-Response Relationship, Drug

Toll-Like Receptors

Flow Cytometry

Time Factors

Receptors, Cell Surface - chemistry

Cell Membrane - metabolism

Receptors, Cell Surface - biosynthesis

Interleukin-8 - metabolism

Respiratory Syncytial Viruses - metabolism

Endotoxins - metabolism

Lung - pathology

Epithelium - metabolism

Cell Separation

Cells, Cultured

Inflammation

Reverse Transcriptase Polymerase Chain Reaction

Blotting, Western

Microscopy, Confocal

Models, Biological

Cell Line, Tumor

Golgi Apparatus - metabolism

Macrophages, Alveolar - cytology

HeLa Cells

Microscopy, Fluorescence

Details

Title: Subtitle: Respiratory syncytial virus up-regulates TLR4 and sensitizes airway epithelial cells to endotoxin
Creators: Martha M Monick - University of Iowa Roy J. and Lucille A. Carver College of Medicine and Veterans Affairs Medical Center, Iowa City, Iowa 52240, USA. martha-monick@uiowa.edu
Timur O Yarovinsky
Linda S Powers
Noah S Butler
A Brent Carter
Gunnar Gudmundsson
Gary W Hunninghake
Resource Type: Journal article
Publication Details: The Journal of biological chemistry, Vol.278(52), pp.53035-53044
DOI: 10.1074/jbc.M308093200
PMID: 14565959
NLM abbreviation: J Biol Chem
ISSN: 0021-9258
eISSN: 1083-351X
Publisher: United States
Grant note: HL-60316 / NHLBI NIH HHS HL073967-01 / NHLBI NIH HHS ES-09607 / NIEHS NIH HHS HL-03860 / NHLBI NIH HHS RR00059 / NCRR NIH HHS
Language: English
Date published: 12/26/2003
Academic Unit: Microbiology and Immunology; Radiation Oncology; Internal Medicine
Record Identifier: 9984001140102771

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