Characterization of epithelial IL-8 response to inflammatory bowel disease mucosal E. coli and its inhibition by mesalamine

Inflamm Bowel Dis. 2008 Feb;14(2):162-75. doi: 10.1002/ibd.20296.


Background: Mucosally adherent E. coli are found in inflammatory bowel disease (IBD) and colon cancer. They promote release of the proinflammatory cytokine interleukin-8 (IL-8). We explored mechanisms for this release and its inhibition by drugs.

Methods: IL-8 release from colon epithelial cells in response to mucosal E. coli isolates from IBD, colon cancer, and controls was characterized at the cellular and molecular level.

Results: IL-8 response of HT29 cells was greater with Crohn's disease (689 +/- 298 [mean +/- SD] pg IL-8/mL at 4 hours, n = 7) and colon cancer isolates (532 +/- 415 pg/mL, n = 14) than with ulcerative colitis (236 +/- 58 pg/mL, n = 6) or control isolates (236 +/- 100 pg/mL, n = 6, P < 0.0001). Bacterial supernatants contained shed flagellin that triggered IL-8 release. For whole bacteria the IL-8 response to E. coli that agglutinate red blood cells (548 +/- 428 pg IL-8/mL, n = 16), a function that correlates with epithelial invasion, was greater than for nonhemagglutinators (281 +/- 253 pg/mL, n = 17; P < 0.0001). This was particularly marked among E. coli that, although flagellate, could not release IL-8 from TLR5-transfected HEK293 cells. IL-8 release was mediated by extracellular-regulated kinase (ERK) and p38 mitogen-activated protein kinase (MAPK) and inhibited by mesalamine, but not hydrocortisone, at therapeutic concentrations.

Conclusions: Mucosa-associated E. coli shed flagellin that elicits epithelial IL-8 release but this may only become relevant when the mucosal barrier is weakened to expose basolateral TLR5. Adherent and invasive IBD and colon cancer E. coli isolates also elicit a flagellin-independent IL-8 response that may be relevant when the mucosal barrier is intact. The IL-8 release is MAPK-dependent and inhibited by mesalamine.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Case-Control Studies
  • Cells, Cultured
  • Colonic Neoplasms / immunology
  • Colonic Neoplasms / microbiology
  • Escherichia coli / drug effects
  • Escherichia coli / genetics
  • Escherichia coli / immunology*
  • Flagellin / genetics
  • Flagellin / immunology
  • Humans
  • Inflammatory Bowel Diseases / immunology*
  • Inflammatory Bowel Diseases / microbiology*
  • Interleukin-8 / antagonists & inhibitors*
  • Interleukin-8 / metabolism*
  • Intestinal Mucosa / immunology
  • Intestinal Mucosa / microbiology
  • MAP Kinase Signaling System
  • Mesalamine / pharmacology*


  • Anti-Inflammatory Agents, Non-Steroidal
  • Interleukin-8
  • Flagellin
  • Mesalamine