Phosphorylation of the epidermal growth factor receptor (EGFR) is essential for interleukin-8 release from intestinal epithelial cells in response to challenge with Escherichia coli O157: H7 flagellin

Fraser-Pitt, D.J., Cameron, P., McNeilly, T.N., Boyd, A., Manson, E.D.T. and Smith, D.G.E. (2011) Phosphorylation of the epidermal growth factor receptor (EGFR) is essential for interleukin-8 release from intestinal epithelial cells in response to challenge with Escherichia coli O157: H7 flagellin. Microbiology, 157(8), pp. 2339-2347. (doi: 10.1099/mic.0.047670-0) (PMID:21546588)

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Abstract

Enterohaemorrhagic <i>Escherichia coli</i> O157 : H7 is a major foodborne and environmental pathogen responsible for both sporadic cases and outbreaks of food poisoning, which can lead to serious sequelae, such as haemolytic uraemic syndrome. The structural subunit of <i>E. coli</i> O157 : H7 flagella is flagellin, which is both the antigenic determinant of the H7 serotype, an important factor in colonization, and an immunomodulatory protein that has been determined to be a major pro-inflammatory component through the instigation of host cell signalling pathways. Flagellin has highly conserved N- and C-terminal regions that are recognized by the host cell pattern recognition receptor Toll-like receptor (TLR) 5. Activation of this receptor triggers cell signalling cascades, which are known to activate host cell kinases and transcription factors that respond with the production of inflammatory mediators such as the chemokine interleukin-8 (IL-8), although the exact components of this pathway are not yet fully characterized. We demonstrate that <i>E. coli</i> O157 : H7-derived flagellin induces rapid phosphorylation of the epidermal growth factor receptor (EGFR), as an early event in intestinal epithelial cell signalling, and that this is required for the release of the pro-inflammatory cytokine IL-8.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Smith, Professor David
Authors: Fraser-Pitt, D.J., Cameron, P., McNeilly, T.N., Boyd, A., Manson, E.D.T., and Smith, D.G.E.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:Microbiology
ISSN:1350-0872
ISSN (Online):1465-2080
Published Online:05 May 2011

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
378891Secretomes of bacterial foodborne pathogens and functional assessment during interaction with intestinal epitheliumDavid SmithBiotechnology and Biological Sciences Research Council (BBSRC)BB/C508485/1Infection Immunity and Inflammation Life Sciences