scholarly journals P051 Macrophages as a source of Notch Ligands in Crohn’s disease: implications in fibrosis

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S159-S160
Author(s):  
M A Jorge ◽  
M D Barrachina ◽  
C Bauset ◽  
L Gisbert-Ferrándiz ◽  
J Cosin-Roger ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Mrna Expression ◽  
Cardiac Fibrosis ◽  
Mrna And Protein Expression ◽  
Fold Induction ◽  
Kidney Liver ◽  
One Way Anova ◽  
Notch Ligands

Abstract Background Fibrosis constitute the main complications associated to Crohn’s disease (CD). Notch signalling has been implicated in lung, kidney, liver and cardiac fibrosis. Macrophages contribute to fibrosis through the release of different mediators and the pattern of secretion may vary according to their microenvironment. The aim of the present study is to analyze the role of Notch ligands derived from macrophages in the complications of CD. Methods We have analyzed: the mRNA expression of cytokines and Notch ligands in CD patients with fistulizing and stenting pattern, the mRNA and protein expression of macrophage markers and Notch ligands in macrophages treated with the main cytokines present in CD patients (IFNγ-, IL10-, IL4, TNFα-U937 treated cells), the mRNA expression of fibrosis markers of DLL4-HT29 treated cells. Results are expressed as fold induction (mean±SEM, n≥4). Statistical analysis was performed with one-way ANOVA followed by Newman-Keuls test. Correlations were analyzed with the Spearman coefficient. Results The mRNA expression of IFNγ, TNFα, IL4, IL6 and IL10 was significantly higher in intestinal samples from B2- and B3-CD patients (11.4±1.6, 6.9±1.3, 16.4±3.9, 4.1±0.4, and 5.0±1.0 respectively for B2, and 14.2±1.8, 9.6±2.6, 21.5±4.1, 6.3±1.0 and 9.2±1.7 respectively for B3) than in controls (1.0±0.09, 1.1±0.2, 1.2±0.1, 1.1±0.1 and 1.0±0.1 respectively). The mRNA expression of DLL3 and DLL4 was significantly higher in intestinal samples from B2 (6.1±1.3 and 9.3±2.4, respectively) than in B3 CD patients (4.4±1.0 and 1.8±0.7, respectively) and in controls (0.9±0.2 and 0.7±1.2 respectively). IFNγ-U937 treated cells increased significantly the mRNA expression of DLL3 and DLL4 (2,9±0,6 N=5 N=4 and 3,7±1,1 N=4, respectively) respect vehicle; IL1β increased significantly the expression of DLL4 (1,8±0,01 N=4) and TNFα increased significantly the expression of DLL3 (7,1±2,2 N=4), respect vehicle. DLL4-HT29 treated cells increased significantly fibrosis markers (VIMENTIN (4,6±0,6 N=6), α-SMA (20,9±8,2 N=6), SNAIL1 (1,8±0,4 N=6), SNAIL2 (8,3±1,3 N=6), ZEB1 (8,2±4,3 N=6) and ZEB2 (4,3±0,2 N=6), respect vehicle. Conclusion Macrophages may act as a source of Notch ligands who could act as fibrosis mediators in CD patients with a stenting (B2) behavior. The microenvironment rich in IFNγ could activate the fibrosis process in epithelial cells by favoring the expression of DLL4 in macrophages.

scholarly journals Differential between Protein and mRNA Expression of CCR7 and SSTR5 Receptors in Crohn's Disease Patients

2009 ◽  
Vol 2009 ◽  
pp. 1-9 ◽  
Author(s):  
Nathalie Taquet ◽  
Serge Dumont ◽  
Jean-Luc Vonesch ◽  
Didier Hentsch ◽  
Jean-Marie Reimund ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Protein Expression ◽  
Mrna Expression ◽  
Large Scale ◽  
Mononuclear Cells ◽  
Biologically Active ◽  
Chronic Inflammatory Bowel Disease ◽  
Peripheral Blood Mononuclear ◽  
Mrna And Protein Expression

Crohn's disease (CD) is a multifactorial chronic inflammatory bowel disease of unknown cause. The aim of the present study was to explore if mRNA over-expression of SSTR5 and CCR7 found in CD patients could be correlated to respective protein expression. When compared to healthy donors, SSTR5 was over-expressed 417±71 times in CD peripheral blood mononuclear cells (PBMCs). Flow cytometry experiments showed no correlation between mRNA and protein expression for SSTR5 in PBMCs. In an attempt to find a reason of such a high mRNA expression, SSTR5 present on CD PBMCs were tested and found as biologically active as on healthy cells. In biopsies of CD intestinal tissue, SSTR5 was not over-expressed but CCR7, unchanged in PBMCs, was over-expressed by 10±3 times in the lamina propria. Confocal microscopy showed a good correlation of CCR7 mRNA and protein expression in CD intestinal biopsies. Our data emphasize flow and image cytometry as impossible to circumvent in complement to molecular biology so to avoid false interpretation on receptor expressions. Once confirmed by further large-scale studies, our preliminary results suggest a role for SSTR5 and CCR7 in CD pathogenesis.

scholarly journals P056 Crohn’s Disease associated fibrosis modulates the expression of collagen receptors

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S163-S163
Author(s):  
S Coll ◽  
C Bauset ◽  
J Cosín-Roger ◽  
D Ortiz-Masià ◽  
L Gisbert-Ferrándiz ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Stromal Cells ◽  
Discoidin Domain Receptors ◽  
Collagen Receptors ◽  
Fibrotic Process ◽  
Fold Induction ◽  
Differential Gene

Abstract Background Crohn’s Disease (CD) patients often develop stenotic complications as immunomodulatory treatments do not prevent the fibrogenic response in the affected tissues, where a dysregulated activation of stromal cells provokes an excessive deposition of extracellular matrix (ECM). Recent evidences support the notion that local cells can sense the consequent alterations in tissue structure and rigidity through receptors that respond to some ECM components, and this may perpetuate the fibrogenic process even in the absence of inflammation. We aim to analyse the relevance of these signalling pathways in the fibrotic process associated to CD. Methods We obtained fibrotic ileal tissues from CD patients and healthy ileal samples from colon carcinoma patients (control), and analysed the expression (RT-PCR, IHQ) of collagen receptors (integrins, discoidin domain receptors/DDR) and of markers for some stromal cells (fibroblasts, endothelial cells). The relationship between these sets of data was analysed by Pearson’s correlation and the results organized as a correlation matrix. The expression of collagen receptors was also analysed in endothelial cells (HUVEC) treated with TGFβ 2 (1ng/ml, 48h). Results Ileal samples from CD patients present a differential gene expression of collagen receptors (Fig 1), with increased levels of ITGA10, ITGA11 and DDR2, and reduced expression of DDR1. In CD tissues, the expression of ITGA11 and DDR1 showed a significant correlation, positive and negative respectively, with that of endothelial markers (Fig 2). These correlations do not occur in control tissues. Integrin-α11 was detected in endothelial cells of submucosal vessels (IHQ). In HUVEC, TGFβ 2 increased the expression of ITGA11 (8.1±0.7 fold induction, p<0.01) and reduced that of DDR1 (0.74±0.06 fold induction, p<0.01), without affecting that of the other collagen receptors. Conclusion Intestinal tissues from CD patients affected by fibrosis present an altered pattern of expression of collagen receptors, which suggests a regulatory role of the ECM in the fibrotic response, while the correlation analysis and the changes induced by the fibrotic cytokine TGFβ in endothelial cells insinuates a particular relevance of these stromal cells in this process.

P056 DISCRIMINATORY ROLE OF ANTI-MICROBIAL ANTIBODIES IN DIAGNOSIS OF CROHN'S DISEASE AGAINST NORMAL AND OTHER MIMICS

2020 ◽  
Vol 158 (3) ◽  
pp. S21-S22
Author(s):  
Peilin Zhang ◽  
Lawrence Minardi ◽  
J. Todd Kuenstner ◽  
Steve Zekan ◽  
Rusty Kruzelock
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease

THE EVALUATION OF SERUM SEROTONIN LEVEL AMONG PATIENTS WITH CROHN’S DISEASE AND ITS IMPACT ON QUALITY OF LIFE

2021 ◽  
Vol 27 (Supplement_1) ◽  
pp. S55-S55
Author(s):  
Marcin Sochal ◽  
Piotr Bialasiewicz ◽  
Agata Gabryelska ◽  
Renata Talar-Wojnarowska ◽  
Jakub Fichna ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Sleep Quality ◽  
Sleep Fragmentation ◽  
Clinical Severity ◽  
Serotonin Level ◽  
Intestinal Physiology ◽  
Tnf Α

Abstract Background and aims Serotonin affects intestinal physiology, mood, as well as circadian rhythm. Moreover, serotonin has proinflammatory function. Therefore, the aim of this study was to investigate the role of serotonin in clinical severity of Crohn’s Disease (CD) and its effect on pain and sleep quality. Methods Fifty-nine CD patients (34 in exacerbation and 25 in remission according to the Harvey-Bradshaw Index-HBI) and 25 health control individuals(HC) were recruited. Sleep quality was assessed by the Pittsburgh Sleep Quality Index (PSQI) and subjective severity of pain by the Visual Analog Scale (VAS). Seventeen patients were treated with anti-TNF-α induction therapy for 14 weeks. Results Serotonin level was higher in CD (145.12ng/mL, IQR:98.14–179.25) compared to HC (87.52ng/mL, IQR:70.04–129.39; p=0.002) and in exacerbation of CD (157.66ng/mL, IQR:111.94–197.64) compared to remission (122.33ng/mL, IQR:83.28–163.67; p=0.029). Serotonin level with cut-off point of 92.45 ng/mL is useful for distinguishing participants with CD from HC (sensitivity: 78%, specificity: 60%, positive predictive value: 82%). Positive correlation between serotonin and HBI (r=0.279, p=0.032) and severity of diarrhoea (r=0.260, p=0.047) were found. Serotonin does not correlate with PSQI (r=0.152, p=0.168), but correlates with presence of sleep fragmentation for example by getting up to use the bathroom (joined 5b-5j PSQI questions; r=0.270, p=0.039). Correlations between serotonin and VAS were also obtained (r=0.220, p=0.045). Moreover, serotonin level significantly decreased after anti-TNF-α therapy (192.35ng/mL, IQR:150.36–225.56 vs. 121.11ng/mL, IQR:91.28–188.87; p=0.006). The study was funded by National Science Centre, Poland (#2018/31/N/NZ5/03715). Conclusions Serotonin level correlates with the severity of CD and decreases after anti-TNF-α therapy. It is associated with sleep fragmentation, which may be caused by diarrhea.

scholarly journals The role of epigenetic modifications for the pathogenesis of Crohn's disease

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
M. Hornschuh ◽  
E. Wirthgen ◽  
M. Wolfien ◽  
K. P. Singh ◽  
O. Wolkenhauer ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Adaptive Immune Response ◽  
Adaptive Immune ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
New Biomarkers ◽  
Insight Into ◽  
Specific Evaluation

AbstractEpigenetics has become a promising field for finding new biomarkers and improving diagnosis, prognosis, and drug response in inflammatory bowel disease. The number of people suffering from inflammatory bowel diseases, especially Crohn's disease, has increased remarkably. Crohn's disease is assumed to be the result of a complex interplay between genetic susceptibility, environmental factors, and altered intestinal microbiota, leading to dysregulation of the innate and adaptive immune response. While many genetic variants have been identified to be associated with Crohn's disease, less is known about the influence of epigenetics in the pathogenesis of this disease. In this review, we provide an overview of current epigenetic studies in Crohn's disease. In particular, we enable a deeper insight into applied bioanalytical and computational tools, as well as a comprehensive update toward the cell-specific evaluation of DNA methylation and histone modifications.

scholarly journals Antagonism of Adherent Invasive E. coli LF82 With Human α-defensin 5 in the Follicle-associated Epithelium of Patients With Ileal Crohn’s Disease

2020 ◽  
Author(s):  
Lina Y Alkaissi ◽  
Martin E Winberg ◽  
Stéphanie DS Heil ◽  
Staffan Haapaniemi ◽  
Pär Myrelid ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Ex Vivo ◽  
Ussing Chambers ◽  
E Coli ◽  
Follicle Associated Epithelium ◽  
Vitro Model ◽  
Set Up

Abstract Background The first visible signs of Crohn’s disease (CD) are microscopic erosions over the follicle-associated epithelium (FAE). The aim of the study was to investigate the effects of human α-defensin 5 (HD5) on adherent-invasive Escherichia coli LF82 translocation and HD5 secretion after LF82 exposure in an in vitro model of human FAE and in human FAE ex vivo. Methods An in vitro FAE-model was set up by the coculture of Raji B cells and Caco-2-cl1 cells. Ileal FAE from patients with CD and controls were mounted in Ussing chambers. The effect of HD5 on LF82 translocation was studied by LF82 exposure to the cells or tissues with or without incubation with HD5. The HD5 secretion was measured in human FAE exposed to LF82 or Salmonella typhimurium. The HD5 levels were evaluated by immunofluorescence, immunoblotting, and ELISA. Results There was an increased LF82 translocation across the FAE-model compared with Caco-2-cl1 (P < 0.05). Incubation of cell/tissues with HD5 before LF82 exposure reduced bacterial passage in both models. Human FAE showed increased LF82 translocation in CD compared with controls and attenuated passage after incubation with sublethal HD5 in both CD and controls (P < 0.05). LF82 exposure resulted in a lower HD5 secretion in CD FAE compared with controls (P < 0.05), whereas Salmonella exposure caused equal secretion on CD and controls. There were significantly lower HD5 levels in CD tissues compared with controls. Conclusions Sublethal HD5 reduces the ability of LF82 to translocate through FAE. The HD5 is secreted less in CD in response to LF82, despite a normal response to Salmonella. This further implicates the integrated role of antimicrobial factors and barrier function in CD pathogenesis.

scholarly journals Role of Probiotics and Their Metabolites in Inflammatory Bowel Diseases (IBDs)

2021 ◽  
Vol 12 (1) ◽  
pp. 56-66
Author(s):  
Toumi Ryma ◽  
Arezki Samer ◽  
Imene Soufli ◽  
Hayet Rafa ◽  
Chafia Touil-Boukoffa
Keyword(s):  
Ulcerative Colitis ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Clinical Symptoms ◽  
Therapeutic Potential ◽  
Short Chain Fatty Acids ◽  
Active Metabolites ◽  
Complex Disorders ◽  
Inflammatory Bowel

Inflammatory Bowel Disease (IBD) is a term used to describe a group of complex disorders of the gastrointestinal (GI) tract. IBDs include two main forms: Crohn’s Disease (CD) and Ulcerative Colitis (UC), which share similar clinical symptoms but differ in the anatomical distribution of the inflammatory lesions. The etiology of IBDs is undetermined. Several hypotheses suggest that Crohn’s Disease and Ulcerative Colitis result from an abnormal immune response against endogenous flora and luminal antigens in genetically susceptible individuals. While there is no cure for IBDs, most common treatments (medication and surgery) aim to reduce inflammation and help patients to achieve remission. There is growing evidence and focus on the prophylactic and therapeutic potential of probiotics in IBDs. Probiotics are live microorganisms that regulate the mucosal immune system, the gut microbiota and the production of active metabolites such as Short-Chain Fatty Acids (SCFAs). This review will focus on the role of intestinal dysbiosis in the immunopathogenesis of IBDs and understanding the health-promoting effects of probiotics and their metabolites.

scholarly journals The multiple faces of inflammatory enteric glial cells: is Crohn’s disease a gliopathy?

2018 ◽  
Vol 315 (1) ◽  
pp. G1-G11 ◽  
Author(s):  
Camille Pochard ◽  
Sabrina Coquenlorge ◽  
Marie Freyssinet ◽  
Philippe Naveilhan ◽  
Arnaud Bourreille ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Glial Cells ◽  
Physiological Role ◽  
Enteric Neurons ◽  
Intestinal Epithelial ◽  
Intestinal Epithelial Barrier ◽  
Enteric Glial Cells ◽  
Glial Reactivity

Gone are the days when enteric glial cells (EGC) were considered merely satellites of enteric neurons. Like their brain counterpart astrocytes, EGC express an impressive number of receptors for neurotransmitters and intercellular messengers, thereby contributing to neuroprotection and to the regulation of neuronal activity. EGC also produce different soluble factors that regulate neighboring cells, among which are intestinal epithelial cells. A better understanding of EGC response to an inflammatory environment, often referred to as enteric glial reactivity, could help define the physiological role of EGC and the importance of this reactivity in maintaining gut functions. In chronic inflammatory disorders of the gut such as Crohn’s disease (CD) and ulcerative colitis, EGC exhibit abnormal phenotypes, and their neighboring cells are dysfunctional; however, it remains unclear whether EGC are only passive bystanders or active players in the pathophysiology of both disorders. The aim of the present study is to review the physiological roles and properties of EGC, their response to inflammation, and their role in the regulation of the intestinal epithelial barrier and to discuss the emerging concept of CD as an enteric gliopathy.

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