Remember Me
Or use your Academic/Social account:


Or use your Academic/Social account:


You have just completed your registration at OpenAire.

Before you can login to the site, you will need to activate your account. An e-mail will be sent to you with the proper instructions.


Please note that this site is currently undergoing Beta testing.
Any new content you create is not guaranteed to be present to the final version of the site upon release.

Thank you for your patience,
OpenAire Dev Team.

Close This Message


Verify Password:
Verify E-mail:
*All Fields Are Required.
Please Verify You Are Human:
fbtwitterlinkedinvimeoflicker grey 14rssslideshare1
Brown, Matthew
Languages: English
Types: Unknown

Classified by OpenAIRE into

mesheuropmc: digestive system diseases, digestive system
Host-microbial interactions are of major importance in the pathogenesis of inflammatory bowel disease (IBD). Toll-like receptors (TLR) are pattern recognition receptors which recognise conserved molecular patterns derived from micro-organisms. Crypt intestinal epithelial cells (IEC) were isolated form mucosal specimens of healthy controls and patients with IBD (ulcerative colitis, UC, and Crohn's disease). A population of IEC enriched for intestinal stem cells (ISC) were identified using Hoechst dye exclusion and by their adherence to cultured primary intestinal myofibroblast cell monolayers. Compared to healthy control colon, TLR2 and TLR4 mRNA and surface protein were significantly up-regulated in crypt IEC isolated from the inflamed mucosa of UC and Crohn's colitis. Compared to healthy control ileum, TLR4 mRNA was significantly up-regulated in crypt epithelial cells isolated from the inflamed mucosa of Crohn‟s ileitis. TLR2 and TLR4 mRNA expression from histologically normal and inflamed colonic mucosa in UC did not significantly differ, and expression of TLR4 transcripts was significantly greater in crypt IEC isolated from histologically normal proximal colonic mucosal samples compared to healthy controls. Myofibroblast-adherent crypt cells expressed TLR2 and TLR4 protein to a greater level than the underlying myofibroblasts. Hoechst-effluxing putative intestinal stem cells expressed both TLR2 and TLR4 transcripts and protein, and TLR3 and TLR5 transcripts. In conclusion, crypt intestinal epithelial cells up-regulated TLR2 and TLR4 expression in UC and Crohn's colitis and up-regulated TLR4 expression in Crohn's ileitis. TLR2 and TLR4 was expressed constitutively in crypt IEC from histologically normal mucosa, suggesting differential TLR expression may in part be a primary event in UC. This provides further insights into the pathogenesis of IBD. Putative intestinal stem cells expressed TLR2, TLR3, TLR4 and TLR5, suggesting that direct microbial sensing by ISC may be important in maintaining intestinal homeostasis and in regulating ISC function.
  • The results below are discovered through our pilot algorithms. Let us know how we are doing!

    • 1. Bray J, Cragg P, Macknight A, Mills R. Lecture notes on human physiology. 4 ed: Blackwell Science Ltd; 1999. 610 p.
    • 2. Podolsky DK. Inflammatory bowel disease. N Engl J Med. 2002;347(6):417-29. Epub 2002/08/09.
    • 3. Loftus EV, Jr. Clinical epidemiology of inflammatory bowel disease: Incidence, prevalence, and environmental influences. Gastroenterology. 2004;126(6):1504-17. Epub 2004/05/29.
    • 4. Probert CS, Brown M. Are there any ethnic groups that are more likely to develop IBD? Inflamm Bowel Dis. 2008;14 Suppl 2:S24-5. Epub 2008/09/26.
    • 5. Hunter MM, McKay DM. Review article: helminths as therapeutic agents for inflammatory bowel disease. Alimentary Pharmacology and Thererapy. 2004;19(2):167-77.
    • 6. Abraham C, Cho JH. Inflammatory bowel disease. N Engl J Med. 2009;361(21):2066-78. Epub 2009/11/20.
    • 7. Bernstein CN, Wajda A, Blanchard JF. The clustering of other chronic inflammatory diseases in inflammatory bowel disease: a population-based study. Gastroenterology. 2005;129(3):827-36. Epub 2005/09/07.
    • 8. Singh S, Graff LA, Bernstein CN. Do NSAIDs, antibiotics, infections, or stress trigger flares in IBD? Am J Gastroenterol. 2009;104(5):1298-313; quiz 314. Epub 2009/04/02.
    • 9. Silverberg MS, Satsangi J, Ahmad T, Arnott ID, Bernstein CN, Brant SR, et al. Toward an integrated clinical, molecular and serological classification of inflammatory bowel disease: Report of a Working Party of the 2005 Montreal World Congress of Gastroenterology. Can J Gastroenterol. 2005;19 Suppl A:5-36. Epub 2005/09/10.
    • 10. Geboes K, van den Oord J, De Wolf-Peeters C, Desmet V, Rutgeerts P, Janssens J, et al. The cellular composition of granulomas in mesenteric lymph nodes from patients with Crohn's disease. Virchows Arch A Pathol Anat Histopathol. 1986;409(5):679-92. Epub 1986/01/01.
    • 11. Quie PG, White JG, Holmes B, Good RA. In vitro bactericidal capacity of human polymorphonuclear leukocytes: diminished activity in chronic granulomatous disease of childhood. J Clin Invest. 1967;46(4):668-79. Epub 1967/04/01.
    • 12. Marks DJ, Harbord MW, MacAllister R, Rahman FZ, Young J, Al-Lazikani B, et al. Defective acute inflammation in Crohn's disease: a clinical investigation. Lancet. 2006;367(9511):668-78. Epub 2006/03/01.
    • 13. Sartor RB. Microbial influences in inflammatory bowel diseases. Gastroenterology. 2008;134(2):577-94. Epub 2008/02/05.
    • 14. Arnott ID, Landers CJ, Nimmo EJ, Drummond HE, Smith BK, Targan SR, et al. Sero-reactivity to microbial components in Crohn's disease is associated with disease severity and progression, but not NOD2/CARD15 genotype. Am J Gastroenterol. 2004;99(12):2376-84. Epub 2004/12/02.
    • 15. Ferrante M, Henckaerts L, Joossens M, Pierik M, Joossens S, Dotan N, et al. New serological markers in inflammatory bowel disease are associated with complicated disease behaviour. Gut. 2007;56(10):1394-403. Epub 2007/04/26.
    • 16. Bossuyt X. Serologic markers in inflammatory bowel disease. Clin Chem. 2006;52(2):171-81. Epub 2005/12/13.
    • 17. Vermeire S, Rutgeerts P. Antibody responses in Crohn's disease. Gastroenterology. 2004;126(2):601-4. Epub 2004/02/06.
    • 18. Targan SR, Landers CJ, Yang H, Lodes MJ, Cong Y, Papadakis KA, et al. Antibodies to CBir1 flagellin define a unique response that is associated independently with complicated Crohn's disease. Gastroenterology. 2005;128(7):2020-8. Epub 2005/06/09.
  • No related research data.
  • No similar publications.

Share - Bookmark

Cite this article