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 (Reading). 2011 Aug;157(Pt 8):2339-2347. doi: 10.1099/mic.0.047670-0. Epub 2011 May 5.

Abstract

Enterohaemorrhagic Escherichia coli 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 E. coli 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 E. coli 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Caco-2 Cells
  • Epithelial Cells / immunology*
  • ErbB Receptors / metabolism*
  • Escherichia coli O157 / immunology*
  • Escherichia coli Proteins / genetics
  • Escherichia coli Proteins / immunology*
  • Flagellin / genetics
  • Flagellin / immunology*
  • Humans
  • Interleukin-8 / metabolism*
  • Intestinal Mucosa / immunology*
  • Phosphorylation
  • Signal Transduction
  • Toll-Like Receptor 5 / immunology

Substances

  • Escherichia coli Proteins
  • FliC protein, E coli
  • Interleukin-8
  • TLR5 protein, human
  • Toll-Like Receptor 5
  • Flagellin
  • ErbB Receptors