Journal
LABORATORY INVESTIGATION
Volume 87, Issue 10, Pages 1042-1054Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/labinvest.3700661
Keywords
inflammatory bowel disease; escherichia coli; invasion; interleukin-8; tumor necrosis factor-alpha; epithelial barrier function
Categories
Funding
- NIDDK NIH HHS [DK064711-03, DK55679, DK0628990-02, DK64399] Funding Source: Medline
- PHS HHS [R24EK064399-04] Funding Source: Medline
Ask authors/readers for more resources
Crohn's disease ( CD) and ulcerative colitis (UC) are idiopathic inflammatory conditions of the gut. Our goal was to investigate if invasive Escherichia coli strains were present in patients with inflammatory bowel disease (IBD). Bacterial strains were isolated from biopsy material obtained from normal controls, and patients with a clinical diagnosis of CD and UC. Invasive bacteria were characterized by gentamicin protection assay and biochemical profiling (Api- 20E). Strains were characterized by induction of cytokine expression in epithelial and macrophage cell cultures, measurement of epithelial barrier function, and confocal microscopy. Of all invasive bacterial strains in CD 98.9% were identified as E. coli as opposed to 42.1% in UC and 2.1% in normal controls. Epithelial invasion in vitro was significantly higher for CD-associated E. coli (8.4%, +/- 5.5 of initial inoculum (I/O)) in comparison to UC (2.5%, +/- 0.4I/O), but highest for strains from inflamed CD tissue (11.3%, +/- 74.3 I/O). Both, CD and UC E. coli strains induced high mean TNF-alpha expression in macrophage cell lines (2604.8 pg/10(5) cells, +/- 447.4; 2,402.6 pg/10(5) cells, +/- 476.3, respectively), but concentrations were significantly higher for isolates from inflamed CD tissue (3071.3 pg/10(5) cells, +/- 226.0). Invasive E. coli from IBD tissue induced similar concentrations of interleukin (IL)-8 in epithelial cell cultures, but strains from inflamed CD tissue induced significantly less epithelial IL-8 (674.1 pg/ 10(5) cells, +/- 58.0 vs 920.5 pg/10(5) cells, +/- 94.6). IBD-associated E. coli strains significantly decreased transepithelial resistance, induced disorganization of F-actin and displacement of ZO-1, and E-cadherin from the apical junctional complex (AJC). In comparison to normal controls and UC, E. coli are more prevalent in CD, are highly invasive, and do not encode for known effector proteins. E. coli strains from IBD patients regulate cytokine expression and epithelial barrier function, two pathological features of IBD.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available