Mucosally adherent E. coli are found in inflammatory bowel disease (IBD) and colon cancer.
They promote release of the proinflammatory cytokine interleukin-8.
Dr Subramanian Sreedhar and colleagues from the United Kingdom explored mechanisms for this release and its inhibition by drugs.
The team characterized interleukin-8 release from colon epithelial cells in response to mucosal E. coli isolates from inflammatory bowel disease, colon cancer, and controls at the cellular and molecular level.
|Mucosa-associated E. coli shed flagellin that elicits epithelial interleukin-8 release|
|Inflammatory Bowel Diseases|
The team found that interleukin-8 response of HT29 cells was greater with Crohn's disease, and colon cancer isolates than with ulcerative colitis or control isolates.
Bacterial supernatants contained shed flagellin that triggered interleukin-8 release.
The team found that for whole bacteria the interleukin-8 response to E. coli that agglutinate red blood cells.
A function that correlates with epithelial invasion, was greater than for nonhemagglutinators.
This was particularly marked among E. coli that, although flagellate, could not release interleukin-8 from TLR5-transfected HEK293 cells.
Interleukin-8 release was mediated by extracellular-regulated kinase and p38 mitogen-activated protein kinase and inhibited by mesalamine, but not hydrocortisone, at therapeutic concentrations.
Dr Sreedhar's team concluded, "Mucosa-associated E. coli shed flagellin that elicits epithelial interleukin-8 release but this may only become relevant when the mucosal barrier is weakened to expose basolateral TLR5."
"Adherent and invasive inflammatory bowel disease and colon cancer E. coli isolates also elicit a flagellin-independent interleukin-8 response that may be relevant when the mucosal barrier is intact."
"The interleukin-8 release is mitogen-activated protein kinase-dependent and inhibited by mesalamine."