scholarly journals WISP1 Is Increased in Intestinal Mucosa and Contributes to Inflammatory Cascades in Inflammatory Bowel Disease

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Qi Zhang ◽  
Cuiping Zhang ◽  
Xiaoyu Li ◽  
Yanan Yu ◽  
Kun Liang ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Mononuclear Cells ◽  
Regulatory Mechanisms ◽  
Matricellular Protein ◽  
Healthy Controls ◽  
Trinitrobenzenesulfonic Acid ◽  
Inflammatory Bowel ◽  
Colonic Biopsies

Inflammatory bowel disease (IBD) is mainly characterized by intestinal tissue damage, which is caused by excessive autoimmune responses poorly controlled by corresponding regulatory mechanisms. WISP1, which belongs to the CCN protein family, is a secreted matricellular protein regulating several inflammatory pathways, such as Wnt/β-catenin pathway, and has been reported in several diseases including cancer. Here we examined the expression, regulatory mechanisms, and functions of WISP1 in IBD. WISP1 mRNA and protein expression was upregulated in colonic biopsies and lamina propria mononuclear cells (LPMC) of IBD patients compared with those of healthy controls. Tumor necrosis factor- (TNF-)αinduced WISP1 expression in LPMC from healthy controls. Consistently, WISP1 mRNA expression was downregulated in colonic biopsies from IBD patients who had achieved clinical remission with infliximab (IFX). Furthermore, WISP1 expression was also found to be increased in colons from 2,4,6-trinitrobenzenesulfonic acid- (TNBS-) induced mice compared with those from control mice. Further studies confirmed that administration of rWISP1 could aggravate TNBS-induced colitis in vivo. Therefore, we concluded that WISP1 is increased in IBD and contributes to the proinflammatory cascades in the gut.

scholarly journals Preclinical Study in Vivo for New Pharmacological Approaches in Inflammatory Bowel Disease: A Systematic Review of Chronic Model of TNBS-Induced Colitis

2019 ◽  
Vol 8 (10) ◽  
pp. 1574 ◽  
Author(s):  
Silva ◽  
Pinto ◽  
Mateus
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Histological Evaluation ◽  
Therapeutic Drug ◽  
Average Dose ◽  
Preclinical Studies ◽  
Trinitrobenzenesulfonic Acid ◽  
Chronic Model ◽  
Inflammatory Bowel

The preclinical studies in vivo provide means of characterizing physiologic interactions when our understanding of such processes is insufficient to allow replacement with in vitro systems and play a pivotal role in the development of a novel therapeutic drug cure. Chemically induced colitis models are relatively easy and rapid to develop. The 2,4,6-trinitrobenzenesulfonic acid (TNBS) colitis model is one of the main models in the experimental studies of inflammatory bowel disease (IBD) since inflammation induced by TNBS mimics several features of Crohn’s disease. This review aims to summarize the existing literature and discuss different protocols for the induction of chronic model of TNBS-induced colitis. We searched MEDLINE via Pubmed platform for studies published through December 2018, using MeSH terms (Crohn Disease.kw) OR (Inflammatory Bowel Diseases.kw) OR (Colitis, Ulcerative.kw) AND (trinitrobenzenesulfonic acid.kw) AND (disease models, animal.kw) AND (mice.all). The inclusion criteria were original articles, preclinical studies in vivo using mice, chronic model of colitis, and TNBS as the inducer of colitis and articles published in English. Chronic TNBS-induced colitis is made with multiple TNBS intrarectal administrations in an average dose of 1.2 mg using a volume lower than 150 μL in 50% ethanol. The strains mostly used are Balb/c and C57BL/6 with 5–6 weeks. To characterize the preclinical model the parameters more used include body weight, stool consistency and morbidity, inflammatory biomarkers like interferon (IFN)-γ, myeloperoxidase (MPO), tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-10, presence of ulcers, thickness or hyperemia in the colon, and histological evaluation of the inflammation. Experimental chronic colitis is induced by multiple rectal instillations of TNBS increasing doses in ethanol using Balb/c and C57BL/6 mice.

scholarly journals Evaluation of Serum Leucine-Rich Alpha-2 Glycoprotein as a New Inflammatory Biomarker of Inflammatory Bowel Disease

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Tetsuhiro Yoshimura ◽  
Keiichi Mitsuyama ◽  
Ryosuke Sakemi ◽  
Hidetoshi Takedatsu ◽  
Shinichiro Yoshioka ◽  
...  
Keyword(s):  
Gene Expression ◽  
Inflammatory Bowel Disease ◽  
Disease Activity ◽  
Bowel Disease ◽  
Mononuclear Cells ◽  
Inflammatory Marker ◽  
Inactive Disease ◽  
Healthy Controls ◽  
Laboratory Parameters ◽  
Inflammatory Bowel

Studies on serum leucine-rich alpha-2 glycoprotein (LRG) in inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD), are scarce; the methods for estimating disease activity are less established, particularly for CD. This study is aimed at evaluating the utility of serum LRG as a potential inflammatory marker for IBD and to investigate the LRG gene expression in peripheral blood mononuclear cells (PBMCs) as a possible source of serum LRG. Overall, 98 patients with UC and 96 patients with CD were prospectively enrolled and clinically evaluated; 92 age-matched individuals served as the healthy controls. The blood samples were analyzed for serum LRG levels and routine laboratory parameters. Disease activity was assessed clinically and endoscopically. Finally, LRG gene expression in the PBMCs from a different cohort (41 patients with UC, 34 patients with CD, and 30 healthy controls) was examined. The serum LRG levels were higher during active disease than during inactive disease; additionally, serum LRG levels were positively correlated with clinical disease activity, C-reactive protein (CRP) levels, and other laboratory parameters in patients with UC and CD and with endoscopic disease activity in UC. UC and CD showed comparable areas under the curve (AUC) values for determining clinical remission and differentiating between endoscopic remission associated with LRG and CRP. The levels of LRG mRNA were also increased in PBMCs from patients with UC and CD and reflected disease activity. These data suggest that serum LRG, originated partially from PBMCs, is an inflammatory marker in UC and CD. A large-scale well-designed study should be conducted in the future to more accurately reveal the clinical significance of LRG in patients with IBD.

scholarly journals OP36 Investigating the role of bioactives produced by gut bacteria to modulate immune response in inflammatory bowel disease

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S037-S038
Author(s):  
R Giri ◽  
K Shamsunnahar ◽  
A Salim ◽  
R Capon ◽  
M Morrison ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Ex Vivo ◽  
Gut Bacteria ◽  
Healthy Controls ◽  
Healthy Human ◽  
Chronic Inflammatory Condition ◽  
Inflammatory Bowel ◽  
Colitis Model

Abstract Background inflammatory bowel disease (IBD) is a chronic inflammatory condition of the gastrointestinal tract. Although the pathogenesis of IBD is not fully understood, it is believed to result from the interaction between various genetic and environmental factors, including the microbiome, resulting in inappropriate gut inflammation. Under homeostatic conditions, the gut immune system exists in a tolerogenic state with the microbiota. However, microbial dysbiosis and an imbalance of pro- and anti-inflammatory cytokines in the gut characterise IBD and recently faecal microbiota transplantation studies have demonstrated that manipulation of the microbiome can induce remission. In this study, the ability of bioactives produced from single species of anaerobic gut bacteria cultured from healthy human faecal samples to modulate NF-kB activity was investigated, their biochemical properties were assessed and their ability to alleviate colitis was also investigated. Methods The NF-κB suppressive effects of culture supernatants (CSs) from 23 different isolates were tested on colonic epithelial cell lines. Suppressive CSs were also tested on human-derived colonic organoids from IBD patients and healthy controls and IL-8 expression was measured. Furthermore, CS from AHG0001 strain was also tested in spontaneous colitis model Winnie in vivo. The supernatant was further characterised by extraction in multiple solvents and fractionated through reversed-phase analytic HPLC column to test for suppressive fractions and further investigate their chemical characteristics. Results LS174T and Caco-2 reporter cells stimulated with TNFα and IL-1β respectively, resulted in NF-κB activation. Of the 23 isolates screened, CS from five isolates significantly suppressed NF-κB activation. The selected CSs also suppressed IL-8 secretion in PBMCs and gut organoids from both UC and CD patients, as well as healthy controls, with notable individual variation. Rectal gavage of CS from AHG0001 also reduced disease activity, improved histologic inflammation and reduced the pro-inflammatory gene expression in Winnie mice. Furthermore, a potent small molecule (IC50 = 3 nM) produced by AHG0001 was also identified through bioassay-guided solvent extractions and filtrations, followed by UPLC-QTOF and comparative metabolomics. Conclusion Our anaerobic culturing and NF-κB reporter assay system allows for the rapid identification of bacteria producing immunomodulatory bioactives, which could lead to the future development of novel therapeutics. Our in vivo and ex vivo testing utilising spontaneous colitis model and patient-derived organoids demonstrates the potential of precision medicine-based approaches for bacterial based therapeutics.

Preparation, characterization, and in vivo evaluation of anti-inflammatory activities of selenium nanoparticles synthesized by Kluyveromyces lactis GG799

2021 ◽  
Author(s):  
Xiao fan Song ◽  
Lei Qiao ◽  
Shuqi Yan ◽  
Yue Chen ◽  
Xina Dou ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Kluyveromyces Lactis ◽  
Selenium Nanoparticles ◽  
Human Diseases ◽  
In Vivo Evaluation ◽  
Inflammatory Bowel ◽  
Anti Inflammatory

Selenium (Se) as an essential micronutrient that has implications in human diseases, including inflammatory bowel disease (IBD), especially with respect to Se deficiencies. Recently, selenium nanoparticles (SeNPs) have attracted significant...

scholarly journals The food additive EDTA aggravates colitis and colon carcinogenesis in mouse models

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Rayko Evstatiev ◽  
Adam Cervenka ◽  
Tina Austerlitz ◽  
Gunther Deim ◽  
Maximilian Baumgartner ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Mouse Models ◽  
Bowel Disease ◽  
Intestinal Inflammation ◽  
Food Additives ◽  
Colorectal Carcinogenesis ◽  
Testing Procedures ◽  
Inflammatory Models ◽  
Inflammatory Bowel

AbstractInflammatory bowel disease is a group of conditions with rising incidence caused by genetic and environmental factors including diet. The chelator ethylenediaminetetraacetate (EDTA) is widely used by the food and pharmaceutical industry among numerous other applications, leading to a considerable environmental exposure. Numerous safety studies in healthy animals have revealed no relevant toxicity by EDTA. Here we show that, in the presence of intestinal inflammation, EDTA is surprisingly capable of massively exacerbating inflammation and even inducing colorectal carcinogenesis at doses that are presumed to be safe. This toxicity is evident in two biologically different mouse models of inflammatory bowel disease, the AOM/DSS and the IL10−/− model. The mechanism of this effect may be attributed to disruption of intercellular contacts as demonstrated by in vivo confocal endomicroscopy, electron microscopy and cell culture studies. Our findings add EDTA to the list of food additives that might be detrimental in the presence of intestinal inflammation, but the toxicity of which may have been missed by regulatory safety testing procedures that utilize only healthy models. We conclude that the current use of EDTA especially in food and pharmaceuticals should be reconsidered. Moreover, we suggest that intestinal inflammatory models should be implemented in the testing of food additives to account for the exposure of this primary organ to environmental and dietary stress.

scholarly journals FOXP3+T Regulatory Cell Modifications in Inflammatory Bowel Disease Patients Treated with Anti-TNFαAgents

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Luisa Guidi ◽  
Carla Felice ◽  
Annabella Procoli ◽  
Giuseppina Bonanno ◽  
Enrica Martinelli ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Inflammatory Bowel Disease ◽  
Flow Cytometry ◽  
Bowel Disease ◽  
Peripheral Blood ◽  
Disease Duration ◽  
Healthy Controls ◽  
T Regulatory Cell ◽  
Inflammatory Bowel ◽  
Necrosis Factor

Treg modulation has been hypothesized as one of the mechanisms by which antitumor necrosis factorα(TNFα) agents exert their action in rheumatoid arthritis (RA) and inflammatory bowel disease (IBD). However, data in IBD are still conflicting. We evaluated CD4+CD25+FOXP3+(Tregs) by flow cytometry in peripheral blood from 32 adult IBD patient before (T0) and after the induction of anti-TNFαtherapy (T1). Eight healthy controls (HCs) were included. We also evaluated the number of FOXP3+cells in the lamina propria (LP) in biopsies taken in a subset of patients and controls. Treg frequencies were significantly increased in peripheral blood from our patients after anti-TNFαtherapy compared to T0. T1 but not T0 levels were higher than HC. The increase was detectable only in clinical responders to the treatment. A negative correlation was found among delta Treg levels and the age of patients or disease duration and with the activity score of Crohn’s disease (CD). No significant differences were found in LP FOXP3+cells. Our data suggest the possibility that in IBD patients the treatment with anti-TNFαmay affect Treg percentages and that Treg modifications may correlate with clinical response, but differently in early versus late disease.

scholarly journals An objective in vivo diagnostic method for inflammatory bowel disease

2018 ◽  
Vol 5 (3) ◽  
pp. 180107 ◽  
Author(s):  
Sophie C. Payne ◽  
Robert K. Shepherd ◽  
Alicia Sedo ◽  
James B. Fallon ◽  
John B. Furness
Keyword(s):  
Inflammatory Bowel Disease ◽  
Real Time ◽  
Bowel Disease ◽  
Experimental Models ◽  
Mucosal Barrier ◽  
Trinitrobenzene Sulfonic Acid ◽  
Inflammatory Damage ◽  
Mucosal Barrier Function ◽  
Inflammatory Bowel

Inflammatory damage to the bowel, as occurs in inflammatory bowel disease (IBD), is debilitating to patients. In both patients and animal experimental models, histological analyses of biopsies and endoscopic examinations are used to evaluate the disease state. However, such measurements often have delays and are invasive, while endoscopy is not quantitatively objective. Therefore, a real-time quantitative method to assess compromised mucosal barrier function is advantageous. We investigated the correlation of in vivo changes in electrical transmural impedance with histological measures of inflammation. Four platinum (Pt) ball electrodes were placed in the lumen of the rat small intestine, with a return electrode under the skin. Electrodes placed within the non-inflamed intestine generated stable impedances during the 3 h testing period. Following an intraluminal injection of 2,4,6-trinitrobenzene sulfonic acid (TNBS), an established animal model of IBD, impedances in the inflamed region significantly decreased relative to a region not exposed to TNBS ( p  < 0.05). Changes in intestinal transmural impedance were correlated ( p  < 0.05) with histologically assessed damage to the mucosa and increases in neutrophil, eosinophil and T-cell populations at 3 h compared with tissue from control regions. This quantitative, real-time assay may have application in the diagnosis and clinical management of IBD.

scholarly journals Fecal Lipocalin-2 as a Sensitive and Noninvasive Biomarker in the TNBS Crohn’s Inflammatory Bowel Disease Model

2016 ◽  
Vol 44 (8) ◽  
pp. 1084-1094 ◽  
Author(s):  
Heidi Hsieh ◽  
Jeffrey Morin ◽  
Cyndi Filliettaz ◽  
Rao Varada ◽  
Shelby LaBarre ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Body Weight ◽  
Bowel Disease ◽  
Saline Water ◽  
Disease Model ◽  
Recovery Phase ◽  
Lipocalin 2 ◽  
Trinitrobenzenesulfonic Acid ◽  
Noninvasive Biomarker ◽  
Inflammatory Bowel

Colitis induced by 2,4,6-Trinitrobenzenesulfonic acid (TNBS) has been used as a model for Crohn’s disease (CD) of inflammatory bowel disease (IBD). Lipocalin-2 (Lcn-2) is an emerging and clinically relevant biomarker of IBD. We investigated the performance of serum and fecal Lcn-2 in the TNBS model of colitis. Female, 7-week-old, BALB/c mice were administered intrarectally phosphate-buffered saline/water or 30% ethanol (vehicle control groups) for 5 days or TNBS for 5 days followed by a 28-day recovery phase. Serum and fecal levels of Lcn-2 were quantified, and effects on body weight, clinical scores, colon weight and length, gross pathology, and histopathology were investigated. Increased serum Lcn-2 levels correlated only with marked to severe inflammation. A clear differentiation in Lcn-2 fecal levels between TNBS-treated and vehicle-treated control mice was most noticeable on days 2 and 3. There was a strong correlation between body weight change, histopathologic scores of inflammation, and/or fecal Lcn-2 levels on days 2 and 5. Both serum and fecal Lcn-2 levels declined over time as the colonic mucosa recovered. Fecal Lcn-2 was found to be a more sensitive biomarker (vs. serum Lcn-2) and was able to discriminate mild, moderate, and severe colonic inflammation.

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