Effect of faecal stream diversion on recurrence of Crohn's disease in the neoterminal ileum

Rutgeerts, Paul; Peeters, Marc; Hiele, Martin; Vantrappen, Gaston; Pennincx, F; Aerts, Raymond; Kerremans, Raymond; Goboes, K

doi:10.1016/0140-6736(91)90663-a

Cited by 716 publications

(380 citation statements)

References 14 publications

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“…Specifically, several lines of evidence point to a dysregulated immune response to a commensal or uncharacterized pathogenic bacteria in the gut. First, patients with inflammatory bowel disease demonstrate immunological reactivity to their own commensal flora (11,12) and fecal diversion is effective in modifying intestinal inflammation (13)(14)(15). Second, manipulation of the bacterial flora either through the use of antibiotics or probiotics is effective in ameliorating inflammatory bowel disease (16 -21).…”

Section: Human Intestinal Epithelial Cells Are Broadly Unresponsive Tmentioning

confidence: 99%

Human Intestinal Epithelial Cells Are Broadly Unresponsive to Toll-Like Receptor 2-Dependent Bacterial Ligands: Implications for Host-Microbial Interactions in the Gut

Melmed¹,

Thomas²,

Lee³

et al. 2003

The Journal of Immunology

396

281

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Intestinal epithelial cells (IEC) interact with a high density of Gram-positive bacteria and are active participants in mucosal immune responses. Recognition of Gram-positive organisms by Toll-like receptor (TLR)2 induces proinflammatory gene expression by diverse cells. We hypothesized that IEC are unresponsive to Gram-positive pathogen-associated molecular patterns and sought to characterize the functional responses of IEC to TLR2-specific ligands. Human colonic epithelial cells isolated by laser capture microscopy and IEC lines (Caco-2, T84, HT-29) were analyzed for expression of TLR2, TLR6, TLR1, and Toll inhibitory protein (Tollip) mRNA by RT-PCR and quantitative real-time PCR. Response to Gram-positive bacterial ligands was measured by NF-κB reporter gene activation and IL-8 secretion. TLR2 protein expression was analyzed by immunofluorescence and flow cytometry. Colonic epithelial cells and lamina propria cells from both uninflamed and inflamed tissue demonstrate low expression of TLR2 mRNA compared with THP-1 monocytes. IECs were unresponsive to TLR2 ligands including the staphylococcal-derived Ags phenol soluble modulin, peptidoglycan, and lipotechoic acid and the mycobacterial-derived Ag soluble tuberculosis factor. Transgenic expression of TLR2 and TLR6 restored responsiveness to phenol soluble modulin and peptidoglycan in IEC. In addition to low levels of TLR2 protein expression, IEC also express high levels of the inhibitory molecule Tollip. We conclude that IEC are broadly unresponsive to TLR2 ligands secondary to deficient expression of TLR2 and TLR6. The relative absence of TLR2 protein expression by IEC and high level of Tollip expression may be important in preventing chronic proinflammatory cytokine secretion in response to commensal Gram-positive bacteria in the gut.

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Section: Human Intestinal Epithelial Cells Are Broadly Unresponsive Tmentioning

confidence: 99%

Human Intestinal Epithelial Cells Are Broadly Unresponsive to Toll-Like Receptor 2-Dependent Bacterial Ligands: Implications for Host-Microbial Interactions in the Gut

Melmed¹,

Thomas²,

Lee³

et al. 2003

The Journal of Immunology

396

281

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“…Moreover, clinical observations show that IBD manifests itself most frequently in the terminal ileum and colon, i.e. those sites with the highest bacterial concentrations in the intestine [9], and that increases in gut permeability precede acute flare-ups in CD [10]. Evidence for the role of the bacterial flora in the induction of experimental colitis is that germ-free or specific pathogen-free animals develop no or less severe inflammation.…”

Section: Introductionmentioning

confidence: 99%

CD4+ T cells from 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis rodents migrate to the recipient's colon upon transfer; down-regulation by CD8+ T cells

Palmen

Wijburg

Kunst

et al. 1998

Clinical and Experimental Immunology

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SUMMARYCD4 þ T cells play an important role in the aetiology of inflammatory bowel disease (IBD), but it is not clear which factor(s) cause activation of these cells. The aim of this study was to examine the effects of adoptive transfer of splenic (CD4 þ ) T cells from TNBS/ethanol-sensitized donor rats to naive recipients and the migration pattern of transferred T cells. For the transfer experiments, colitis was induced in rats by colonic administration of TNBS/ethanol. Seventeen days later, either total splenic T cells or CD4 þ , or CD8 þ T cells were transferred to naive recipients. At days 1, 2 and 3 after transfer, the recipients were killed and the migration pattern of the transferred T cells was studied, as well as inflammatory cells in several organs, including the colon. To determine cytokine profiles of the T cells, colitis was induced in mice. Therefore, different combinations of 2,4-dinitrobenzene sulfonic acid (DNBS) in ethanol or saline, or ethanol alone were intrarectally administered. At day 9 after induction of colitis, mice were killed and cytokine profiles in the colon were studied by reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry. The results show that CD4 þ T cells from donor rats with TNBS/ ethanol-induced colitis migrate in particular to the colon upon transfer to naive recipients, and that this process is down-regulated by CD8 þ T cells. This migration is probably caused by T cell recognition of the colonic bacterial flora and initiates an inflammatory reaction in the recipient's colon, characterized by an increase of the recipient's own T cells, macrophages, and neutrophils. In the mice experiments we showed that a second administration of DNBS/ethanol or ethanol alone, which presumably causes bacterial translocation, results in increased numbers of T cells into the colon, accompanied by an increase in Th1 cytokines. These data suggest that Th1 cells recognize the colonic bacterial flora.

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“…In support of this, it has been shown that antibiotics dampen the symptoms of Crohn's patients and the effect is reversed when treatment is terminated [5]. Also, clinical experiments in patients with active colonic disease where the fecal stream was diverted by a proximal ileostomy led to resolution of the inflammation, but the patients suffered a relapse when the bowel luminal contents were re-introduced [6,7]. In addition, it has been shown that Crohn's patients have a defect in bacterial clearance [8] and polymorphisms in receptors that recognize bacteria are overrepresented in patients [3,4].…”

Section: Overreactivity To Intestinal Bacteria Underlies Crohn's Diseasementioning

confidence: 94%

Intestinal dendritic cell and macrophage subsets: Tipping the balance to Crohn's Disease?

Magnusson

Wick

2011

European Journal of Microbiology and Immunology

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Effect of faecal stream diversion on recurrence of Crohn's disease in the neoterminal ileum

Cited by 716 publications

References 14 publications

Human Intestinal Epithelial Cells Are Broadly Unresponsive to Toll-Like Receptor 2-Dependent Bacterial Ligands: Implications for Host-Microbial Interactions in the Gut

Human Intestinal Epithelial Cells Are Broadly Unresponsive to Toll-Like Receptor 2-Dependent Bacterial Ligands: Implications for Host-Microbial Interactions in the Gut

CD4+ T cells from 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis rodents migrate to the recipient's colon upon transfer; down-regulation by CD8+ T cells

Intestinal dendritic cell and macrophage subsets: Tipping the balance to Crohn's Disease?

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