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

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.

The TGFα-EGFR-Akt signaling axis plays a role in enhancing proinflammatory chemokines in triple-negative breast cancer cells

“…In bronchial epithelial cells, 1-nitropyrene/1-aminopyrene and airborne particulates induce CXCL8 expression via the TGFα-EGFR signaling pathway [ 74 , 75 ]. EGFR activation is essential for CXCL8 release from intestinal epithelial cells in response to challenge by Escherichia coli O157:H7 flagellin [ 76 ]. All these previous reports support our current observation that CXCL1 and 8 are the dominant chemokines in TNBC cells which express high levels of EGFR.…”

Pathogenesis of Human Enterovirulent Bacteria: Lessons from Cultured, Fully Differentiated Human Colon Cancer Cell Lines

“…The MAPK and NF-B pathways leading to IL-8 secretion are also activated by isolated EHEC H7 flagellin added to either the apical or basolateral surface of fully differentiated Caco-2 cells (784). The EHEC H7 flagellin-induced production of IL-8 in fully differentiated Caco-2 cells develops together with the phosphorylation of the epidermal growth factor receptor (786). Moreover, EHEC expressing HCP induces significant release of IL-8 and TNF-␣, but not of IL-2, IL-6, or IL-10, in fully differentiated T84 cells via Erk1/2, p38, and JNK MAPK signaling activation (787).…”

Immunobiotic Strains Modulate Toll-Like Receptor 3 Agonist Induced Innate Antiviral Immune Response in Human Intestinal Epithelial Cells by Modulating IFN Regulatory Factor 3 and NF-κB Signaling

“…Intestinal epithelium contains IECs, which play important roles in maintenance of the intestinal immune system. Upon meeting pathogens, IECs capable to induce mucosal immune responses by expressing soluble factors such as cytokines/chemokines to recruit and activate immune cells including leukocytes and neutrophil granulocytes to the infected area, and by producing type I IFNs, antiviral proteins, and effector molecules to limit pathogens replications (25, 26). The expressions of TLRs in IECs play an important role on induction of mucosal immune responses in the intestine by sensing antigens derived from pathogens during their infection.…”