OP20 TNF and MDP induce epithelial-to-mesenchymal transition in human intestinal cells: Implications for the pathogenesis of Crohn's disease-associated fistulae and the use of anti-TNF antibodies

2012 ◽  
Vol 6 ◽  
pp. S10 ◽  
Author(s):  
M. Scharl ◽  
S. Frei ◽  
T. Pesch ◽  
S. Kellermeier ◽  
A. Weber ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Epithelial To Mesenchymal Transition ◽  
Intestinal Cells ◽  
Mesenchymal Transition ◽  
Human Intestinal Cells

scholarly journals Succinate Activates EMT in Intestinal Epithelial Cells through SUCNR1: A Novel Protagonist in Fistula Development

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1104 ◽  
Author(s):  
Dolores Ortiz-Masiá ◽  
Laura Gisbert-Ferrándiz ◽  
Cristina Bauset ◽  
Sandra Coll ◽  
Céline Mamie ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Epithelial Cells ◽  
Wnt Signaling ◽  
Intestinal Inflammation ◽  
Intestinal Epithelial Cells ◽  
Fistula Tract ◽  
Intestinal Epithelial ◽  
Mesenchymal Transition ◽  
Ht29 Cells

The pathogenesis of Crohn’s disease-associated fibrostenosis and fistulas imply the epithelial-to-mesenchymal transition (EMT) process. As succinate and its receptor (SUCNR1) are involved in intestinal inflammation and fibrosis, we investigated their relevance in EMT and Crohn’s disease (CD) fistulas. Succinate levels and SUCNR1-expression were analyzed in intestinal resections from non-Inflammatory Bowel Disease (non-IBD) subjects and CD patients with stenosing-B2 or penetrating-B3 complications and in a murine heterotopic-transplant model of intestinal fibrosis. EMT, as increased expression of Snail1, Snail2 and vimentin and reduction in E-cadherin, was analyzed in tissues and succinate-treated HT29 cells. The role played by SUCNR1 was studied by silencing its gene. Succinate levels and SUCNR1 expression are increased in B3-CD patients and correlate with EMT markers. SUCNR1 is detected in transitional cells lining the fistula tract and in surrounding mesenchymal cells. Grafts from wild type (WT) mice present increased succinate levels, SUCNR1 up-regulation and EMT activation, effects not observed in SUCNR1−/− tissues. SUCNR1 activation induces the expression of Wnt ligands, activates WNT signaling and induces a WNT-mediated EMT in HT29 cells. In conclusion, succinate and its receptor are up-regulated around CD-fistulas and activate Wnt signaling and EMT in intestinal epithelial cells. These results point to SUCNR1 as a novel pharmacological target for fistula prevention.

scholarly journals Lactobacillus casei DN-114 001 Inhibits the Ability of Adherent-Invasive Escherichia coli Isolated from Crohn's Disease Patients To Adhere to and To Invade Intestinal Epithelial Cells

2005 ◽  
Vol 71 (6) ◽  
pp. 2880-2887 ◽  
Author(s):  
Isabelle Ingrassia ◽  
Antony Leplingard ◽  
Arlette Darfeuille-Michaud
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Epithelial Cells ◽  
Lactobacillus Casei ◽  
Intestinal Epithelial Cells ◽  
Probiotic Strain ◽  
Intestinal Cells ◽  
Intestinal Epithelial ◽  
Inhibitory Effects ◽  
E Coli

ABSTRACT Ileal lesions in 36.4% of patients with Crohn's disease are colonized by pathogenic adherent-invasive Escherichia coli. The aim of this study was to determine the in vitro inhibitory effects of the probiotic strain, Lactobacillus casei DN-114 001, on adhesion to and invasion of human intestinal epithelial cells by adherent-invasive E. coli isolated from Crohn's disease patients. The experiments were performed with undifferentiated Intestine-407 cells and with undifferentiated or differentiated Caco-2 intestinal epithelial cells. Bacterial adhesion to and invasion of intestinal epithelial cells were assessed by counting CFU. The inhibitory effects of L. casei were determined after coincubation with adherent-invasive E. coli or after preincubation of intestinal cells with L. casei prior to infection with adherent-invasive E. coli. Inhibitory effects of L. casei on adherent-invasive E. coli adhesion to differentiated and undifferentiated intestinal epithelial cells reached 75% to 84% in coincubation and 43% to 62% in preincubation experiments, according to the cell lines used. Addition of L. casei culture supernatant to the incubation medium increased L. casei adhesion to intestinal epithelial cells and enhanced the inhibitory effects of L. casei. The inhibitory effects on E. coli invasion paralleled those on adhesion. This effect was not due to a bactericidal effect on adherent-invasive E. coli or to a cytotoxic effect on epithelial intestinal cells. As Lactobacillus casei DN-114 001 strongly inhibits interaction of adherent-invasive E. coli with intestinal epithelial cells, this finding suggests that the probiotic strain could be of therapeutic value in Crohn's disease.

scholarly journals Ileal Inflammation May Trigger the Development of GP2-Specific Pancreatic Autoantibodies in Patients with Crohn’s Disease

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Polychronis Pavlidis ◽  
Ourania Romanidou ◽  
Dirk Roggenbuck ◽  
Maria G. Mytilinaiou ◽  
Faris Al-Sulttan ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Surgical Intervention ◽  
Intestinal Cells ◽  
Apical Surface ◽  
Humoral Autoimmunity ◽  
Bowel Diseases ◽  
Antigenic Source ◽  
Inflammatory Bowel ◽  
Major Target

Why zymogen glycoprotein 2 (GP2), the Crohn’s disease (CD)-specific pancreatic autoantigen, is the major target of humoral autoimmunity in inflammatory bowel diseases (IBD) is uknown. Recent evidence demonstrates that GP2 is also present on the apical surface of microfold (M) intestinal cells. As the colon lacks GP2-rich M cells, we assumed that patients with colonic CD are seronegative for anti-GP2. Anti-GP2 antibodies were tested in 225 CDs, including 45 patients with colonic location (L2), 45 with terminal ileum (L1) and 135 with ileocolonic involvement; 225 patients with ulcerative colitis (UC) were also tested. Anti-GP2 reactivity was detected in 59 (26.2%) CDs and 15 (6.7%) UCs(P<0.001). Only 5 CDs with L2 had anti-GP2 antibodies, compared to 54/180 (30.0%,P=0.0128) of the CDs with L1 and L3. Anti-GP2 antibody positive CD patients had higher ASCA titres compared to seronegative cases. Amongst the 128 CD patients with previous surgical intervention, 45 (35.0%) were anti-GP2 antibody positive compared to 14/97 (14.0%) without surgical(P<0.001). Our data support the assumption that ileal inflammation is required for the development of anti-GP2 antibodies in CD, and suggest that the intestine rather than the pancreatic juice is the antigenic source required for the initiation of anti-GP2 antibodies.

Proteomics Highlights Common and Distinct Pathophysiological Processes Associated with Ileal and Colonic Ulcers in Crohn’s Disease

2019 ◽  
Vol 14 (2) ◽  
pp. 205-215 ◽  
Author(s):  
Nicolas Pierre ◽  
Catherine Salée ◽  
Charlotte Massot ◽  
Noëlla Blétard ◽  
Gabriel Mazzucchelli ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Epithelial Mesenchymal Transition ◽  
Colonic Disease ◽  
Differential Proteomics ◽  
Tissue Samples ◽  
Mesenchymal Transition ◽  
Colonic Ulcer ◽  
Endoplasmic Reticulum Protein

Abstract Background and Aims Based on genetics and natural history, Crohn’s disease can be separated into two entities, an ileal and a colonic disease. Protein-based approaches are needed to elucidate whether such subphenotypes are related to distinct pathophysiological processes. Methods The proteome of ulcer edges was compared with that of paired control tissue samples [n = 32 biopsies] by differential proteomics in the ileum and the colon of Crohn’s disease patients [n = 16]. The results were analysed using a hypothesis-driven approach [based on the literature] and a hypothesis-free approach [pathway enrichment analyses] to determine common and segment-specific pathophysiological processes associated with ileal and colonic CD ulcer edges. To confirm the involvement of a key pathway highlighted by proteomics, two proteins were also studied by immunochemistry. Results In the ileum and the colon, 4428 and 5204 proteins, respectively, were identified and quantified. Ileal and colonic ulcer edges differed in having a distinct distribution of proteins associated with epithelial–mesenchymal transition, neutrophil degranulation, and ribosomes. Ileal and colonic ulcer edges were similarly characterized by an increase in the proteins implicated in the endoplasmic reticulum protein-processing pathway and a decrease in mitochondrial proteins. Immunochemistry confirmed the presence of endoplasmic reticulum stress in the mucosa of ileal and colonic ulcer edges. Conclusion This study provides protein-based evidence for partially distinct pathophysiological processes being associated with ileal and colonic ulcer edges in Crohn’s disease patients. This could constitute a first step toward the development of gut segment–specific diagnostic markers and therapeutics.

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