Characterization of epithelial IL-8 response to inflammatory bowel disease mucosal E. coli and its inhibition by mesalamine
✍ Scribed by Sreedhar Subramanian; Jonathan M. Rhodes; C. Anthony Hart; Ben Tam; Carol L. Roberts; Shirley L. Smith; John E. Corkill; Craig Winstanley; Mumtaz Virji; Barry J. Campbell
- Book ID
- 102265988
- Publisher
- John Wiley and Sons
- Year
- 2008
- Tongue
- English
- Weight
- 492 KB
- Volume
- 14
- Category
- Article
- ISSN
- 1078-0998
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✦ Synopsis
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.