Activation of the epidermal growth factor receptor by respiratory syncytial virus results in increased inflammation and delayed apoptosis

Martha M Monick; Kelli Cameron; Janice Staber; Linda S Powers; Timur O Yarovinsky; John G Koland; Gary W Hunninghake

doi:10.1074/jbc.M408745200

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Activation of the epidermal growth factor receptor by respiratory syncytial virus results in increased inflammation and delayed apoptosis

Journal article

Open access

Peer reviewed

Activation of the epidermal growth factor receptor by respiratory syncytial virus results in increased inflammation and delayed apoptosis

Martha M Monick, Kelli Cameron, Janice Staber, Linda S Powers, Timur O Yarovinsky, John G Koland and Gary W Hunninghake

The Journal of biological chemistry, Vol.280(3), pp.2147-2158

01/21/2005

DOI: 10.1074/jbc.M408745200

PMID: 15542601

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Abstract

Respiratory syncytial virus (RSV) preferentially infects lung epithelial cells. Infection by RSV leads to an extended inflammatory response, characterized by the release of interleukin-8 (IL-8). Activation of ERK MAP kinase is required for both RSV-induced inflammation and the extended survival of infected cells. In this study, we analyzed the role of the epidermal growth factor receptor (EGFR) in RSV activation of ERK. We demonstrate for the first time that RSV activates EGFR in lung epithelial cells. Activation of EGFR results in increased ERK activity, contributing to both the inflammatory response (IL-8 release) and prolonging the survival of RSV-infected cells. Inhibition of EGFR with siRNA decreased both ERK activation and IL-8 production after RSV. In analyzing the effect of EGFR activation on survival of RSV-infected cells, we found that EGFR activation by RSV resulted in ERK-dependent alterations in the balance of pro- versus anti-apoptotic Bcl2 proteins. RSV altered the balance between pro- and anti-apoptotic Bcl2 proteins (increased BclxL and decreased BimEL) increasing the relative amount of pro-survival proteins. This occurred in an EGFR-dependent manner. This study supports an important role for EGFR activity in the lifespan and inflammatory potential of RSV-infected epithelial cells.

Cell Line

Inflammation - metabolism

ErbB Receptors - metabolism

Immunoprecipitation

Respiratory Syncytial Viruses - physiology

Virus Replication

Interleukin-8 - biosynthesis

Humans

RNA, Messenger - genetics

ErbB Receptors - genetics

Apoptosis

Details

Title: Subtitle: Activation of the epidermal growth factor receptor by respiratory syncytial virus results in increased inflammation and delayed apoptosis
Creators: Martha M Monick - Department of Internal Medicine, University of Iowa Carver College of Medicine and Veterans Administration Medical Center, Iowa City, Iowa 52242, USA. martha-monick@uiowa.edu
Kelli Cameron
Janice Staber
Linda S Powers
Timur O Yarovinsky
John G Koland
Gary W Hunninghake
Resource Type: Journal article
Publication Details: The Journal of biological chemistry, Vol.280(3), pp.2147-2158
DOI: 10.1074/jbc.M408745200
PMID: 15542601
NLM abbreviation: J Biol Chem
ISSN: 0021-9258
eISSN: 1083-351X
Publisher: United States
Grant note: HL-60316 / NHLBI NIH HHS RR00059 / NCRR NIH HHS HL-077431 / NHLBI NIH HHS
Language: English
Date published: 01/21/2005
Academic Unit: Pulmonary, Critical Care, and Occupational Medicine; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Hematology/Oncology; Neuroscience and Pharmacology; Internal Medicine
Record Identifier: 9984065829002771

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