TITLE

Lipopolysaccharide modulation of normal enterocyte turnover by toll-like receptors is mediated by endogenously produced tumour necrosis factors α

AUTHOR(S)
Ruemmele, F.M.; Beaulieu, J.F.; Dionne, S.; Levy, E.; Seidman, E.G.; Cerf-Bensussan, N.; Lentze, M.J.
PUB. DATE
December 2002
SOURCE
Gut;Dec2002, Vol. 51 Issue 6, p842
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Background: Circulating levels of endotoxin (or lipopolysaccharide (LPS)) and anti-endotoxin antibodies are increased in patients with inflammatory bowel disease, supporting the hypothesis of a role for endogenous bacterial products in the pathogenesis of these disorders. Aim: The aim of this study was to analyse the direct effects of LPS on intestinal epithelial cell turnover. Methods and Results: LPS significantly inhibited growth of the human non-transformed immature crypt cell line (HIEC), whereas IEC-6 cell proliferation was stimulated by LPS. As LPS is a physiological inducer of tumour necrosis factor α (TNFα) in various cell systems and this cytokine exerted similar antiproliferative (HIEC) or growth stimulatory (IEC-6 cells) effects, the study thus tested the hypothesis that endogenously produced TNFα in response to LPS mediates this growth modulatory effect in an autoparacrine/paracrine way. Therefore, during LPS stimulation, the biological activity of TNFα was blocked using neutralising anti-TNFα antibodies, as well as inhibitory, antagonistic antibodies directed against the p55 TNF receptor, signalling the antimitotic TNFα effect in HIEC. Both experimental approaches completely abolished the growth modulatory effects of LPS in HIEC/IEC-6 cells. Production and secretion of TNFα by HIEC/IEC-6 cells in response to LPS was confirmed on mRNA and protein level by reverse transcription polymerase chain reaction (RT-PCR) and enzyme linked immunosorbent assay. LPS signalling was independent of CD14 in HIEC, as these cells lack this receptor. However, HIEC expressed TLR4 and MD2 resulting in a fully functional signalling complex as demonstrated by RT-PCR, western blot, and immunofluorescence analyses. Conclusion: These results support the hypothesis that LPS induced changes of intestinal epithelial cell turnover may directly contribute to the pathogenesis of inflammatory epithelial cell lesions by endogenous TNFα...
ACCESSION #
9737562

 

Related Articles

  • A place for TACE. van Deventer, S.J.H. // Gut;Jul2002, Vol. 51 Issue 1, p5 

    Comments on a study by J. Brynskov and colleagues, which examined tumor necrosis factor-alpha converting enzyme (TACE) activity in the colonic mucosa of patients with inflammatory bowel disease. Control of the production and secretion of TNA-alpha at multiple checkpoints; Physiological...

  • Tumour necrosis factor α converting enzyme (TACE) activity in the colonic mucosa of patients with inflammatory bowel disease. Brynskov, J.; Foegh, P.; Pedersen, G.; Ellervik, C.; Kirkegaard, T.; Bingham, A.; Saermark, T. // Gut;Jul2002, Vol. 51 Issue 1, p37 

    Background: Anti-tumour necrosis factor α (TNF-α) antibodies are effective in Crohn's disease and perhaps ulcerative colitis but antigenicity and the high cost have raised interest in other strategies to block TNF-α. These include the TNF-α converting enzyme (TACE) which releases...

  • Control of matrix metalloproteinase production in human intestinal fibroblasts by interleukin 21. Monteleone, G.; Caruso, R.; Fina, D.; Peluso, I.; Gioia, V.; Stolfi, C.; Fantini, M. C.; Caprioli, F.; Tersigni, R.; Alessandroni, L.; MacDonald, T. T.; Pallone, F. // Gut;Dec2006, Vol. 55 Issue 12, p1774 

    Background: T cell-mediated immunity plays a central part in the pathogenesis of tissue damage in inflammatory bowel disease (IBD). The mechanism by which T cells mediate tissue damage during IBD remains unclear, but evidence indicates that T cell-derived cytokines stimulate fibroblasts to...

  • Biologic response modifiers to decrease inflammation: Focus on infection risks. Saux, Nicole Le // Paediatrics & Child Health (1205-7088);Mar2012, Vol. 17 Issue 3, p147 

    Biologic response modifiers are a novel class of drugs used by sub-specialists to treat immune-mediated conditions such as juvenile idiopathic arthritis and inflammatory bowel disease. Also known as 'cytokine inhibitors', they are proteins whose purpose is to block the action of cytokines...

  • The classics in perspective. Panés, Julián; Ghosh, Subrata // Gut;Sep2007, Vol. 56 Issue 9, p1184 

    The authors reflect on the development of anti-cytokine therapies as biological agents in treating Crohn's disease and inflammatory diseases. Their therapeutic approach to these diseases has expanded. They noted that gastroenterologists face a remarkable wave of new biological therapies for...

  • Infliximab for the treatment of pyrodema gangrenosum: a randomised, double blind, placebo controlled trial. Brooklyn, T. N.; Dunnill, M. G. S.; Shetty, A.; Bowden, J. J.; Williams, J. D. L.; Griffiths, C. E. M.; Forbes, A.; Greenwood, R.; Probert, C. S. // Gut;Apr2006, Vol. 55 Issue 4, p505 

    Background: Pyoderma gangrenosum (PG) is a chronic ulcerating skin condition that often occurs in association with inflammatory bowel disease. There have been a number of reports of PG responding to infliximab, a monoclonal antibody against tumour necrosis factor α. Aim: In the first...

  • Increased expression of tumor necrosis factor-α messenger RNA in the intestinal mucosa of inflammatory bowel disease, particularly in patients with disease in the inactive phase. Akazawa, Akiko; Sakaida, Isao; Higaki, Shingo; Kubo, Yoshitsugu; Uchida, Koichi; Okita, Kiwamu // Journal of Gastroenterology;2002, Vol. 37 Issue 5, p345 

    Background: Tumor necrosis factor-α (TNF-α), may be involved in the pathogenesis of inflammatory bowel diseases (IBDs). The aim of this study was to evaluate the effect of TNF-α on the inflammatory activity of IBD. Methods: TNF-α mRNA expression in intestinal mucosal biopsy specimens...

  • CORRECTION.  // Gut;Nov2004, Vol. 53 Issue 11, p1722 

    Several corrections to the articles including "Downregulation of epithelial apoptosis and barrier repair in active Crohn's disease by tumour necrosis factor antibody treatment," by S. J. Connor, "Morphological characterisation of Crohn's disease fistulae," by F. Bataille, and "Divergent patterns...

  • Hepatosplenic T cell lymphoma in inflammatory bowel disease. Shale, Matthew; Kanfer, Ed; Panaccione, Remo; Ghosh, Subrata // Gut;Dec2008, Vol. 57 Issue 12, p1639 

    The article discusses the enhancement of lymphoma in inflammatory bowel disease (IBD). It mentions that thiopurine therapy has possibility to cause risk of lynmphoma. The experts state the appearance of hepatosplenic T cell lymphoma (HSTCL) in the patients of IBD who are displayed with...

Share

Read the Article

Courtesy of VIRGINIA BEACH PUBLIC LIBRARY AND SYSTEM

Sign out of this library

Other Topics