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

2.50
Hdl Handle:
http://hdl.handle.net/2336/15743
Title:
Respiratory syncytial virus up-regulates TLR4 and sensitizes airway epithelial cells to endotoxin
Authors:
Monick, Martha M; Yarovinsky, Timur O; Powers, Linda S; Butler, Noah S; Carter, A Brent; Gudmundsson, Gunnar; Hunninghake, Gary W
Citation:
J. Biol. Chem. 2003, 278(52):53035-44
Issue Date:
26-Dec-2003
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.
Description:
To access publisher full text version of this article. Please click on the hyperlink in Additional Links field
Additional Links:
http://www.jbc.org/cgi/content/abstract/278/52/53035

Full metadata record

DC FieldValue Language
dc.contributor.authorMonick, Martha M-
dc.contributor.authorYarovinsky, Timur O-
dc.contributor.authorPowers, Linda S-
dc.contributor.authorButler, Noah S-
dc.contributor.authorCarter, A Brent-
dc.contributor.authorGudmundsson, Gunnar-
dc.contributor.authorHunninghake, Gary W-
dc.date.accessioned2008-01-07T14:30:07Z-
dc.date.available2008-01-07T14:30:07Z-
dc.date.issued2003-12-26-
dc.date.submitted2007-01-07-
dc.identifier.citationJ. Biol. Chem. 2003, 278(52):53035-44en
dc.identifier.issn0021-9258-
dc.identifier.pmid14565959-
dc.identifier.doi10.1074/jbc.M308093200-
dc.identifier.urihttp://hdl.handle.net/2336/15743-
dc.descriptionTo access publisher full text version of this article. Please click on the hyperlink in Additional Links fielden
dc.description.abstractAirway 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.en
dc.language.isoenen
dc.publisherAmerican Society for Biochemistry and Molecular Biologyen
dc.relation.urlhttp://www.jbc.org/cgi/content/abstract/278/52/53035en
dc.subject.meshBlotting, Westernen
dc.subject.meshCell Line, Tumoren
dc.subject.meshCell Membraneen
dc.subject.meshCell Separationen
dc.subject.meshCells, Cultureden
dc.subject.meshCross-Linking Reagentsen
dc.subject.meshDose-Response Relationship, Drugen
dc.subject.meshEndotoxinsen
dc.subject.meshEpithelial Cellsen
dc.subject.meshEpitheliumen
dc.subject.meshFlow Cytometryen
dc.subject.meshGolgi Apparatusen
dc.subject.meshHela Cellsen
dc.subject.meshHumansen
dc.subject.meshInflammationen
dc.subject.meshInterleukin-8en
dc.subject.meshLipopolysaccharidesen
dc.subject.meshLungen
dc.subject.meshMAP Kinase Signaling Systemen
dc.subject.meshMacrophages, Alveolaren
dc.subject.meshMembrane Glycoproteinsen
dc.subject.meshMicroscopy, Confocalen
dc.subject.meshMicroscopy, Fluorescenceen
dc.subject.meshModels, Biologicalen
dc.subject.meshMonocytesen
dc.subject.meshRNA, Messengeren
dc.subject.meshReceptors, Cell Surfaceen
dc.subject.meshRespiratory Syncytial Virusesen
dc.subject.meshReverse Transcriptase Polymerase Chain Reactionen
dc.subject.meshTime Factorsen
dc.subject.meshToll-Like Receptor 4en
dc.subject.meshToll-Like Receptorsen
dc.subject.meshTumor Necrosis Factor-alphaen
dc.subject.meshUp-Regulationen
dc.titleRespiratory syncytial virus up-regulates TLR4 and sensitizes airway epithelial cells to endotoxinen
dc.typeArticleen
dc.contributor.departmentDepartment of Medicine, National University Hospital, IS-101 Reykjavik, Icelanden
dc.identifier.journalJournal of biological chemistryen

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