Differential expression of TGF-β isoforms by normal and inflammatory bowel disease intestinal myofibroblasts

2002 ◽  
Vol 282 (1) ◽  
pp. C172-C182 ◽  
Author(s):  
B. C. McKaig ◽  
K. Hughes ◽  
P. J. Tighe ◽  
Y. R. Mahida
Keyword(s):  
Ulcerative Colitis ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Wound Repair ◽  
Transforming Growth Factor ◽  
Intestinal Epithelial Cells ◽  
Intestinal Epithelial ◽  
Proliferative Capacity ◽  
Inflammatory Bowel ◽  
Lower Expression

First published September 5, 2001; 10.1152/ajpcell. 00048.2001.—Intestinal strictures are frequent in Crohn's disease but not ulcerative colitis. We investigated the expression of transforming growth factor (TGF)-β isoforms by isolated and cultured primary human intestinal myofibroblasts and the responsiveness of these cells and intestinal epithelial cells to TGF-β isoforms. Normal intestinal myofibroblasts released predominantly TGF-β3 and ulcerative colitis myofibroblasts expressed both TGF-β1 and TGF-β3, whereas in myofibroblast cultures from fibrotic Crohn's disease tissue, there was significantly lower expression of TGF-β3 but enhanced release of TGF-β2. These distinctive patterns of TGF-β isoform release were sustained through several myofibroblast passages. Proliferation of Crohn's disease myofibroblasts was significantly greater than that of myofibroblasts derived from normal and ulcerative colitis tissue. In contrast to cells from normal and ulcerative colitis tissue, neutralization of the three TGF-β isoforms did not affect the proliferation of Crohn's disease intestinal myofibroblasts. Studies on the effect of recombinant TGF-β isoforms on epithelial restitution and proliferation suggest that TGF-β2 may be the least effective of the three isoforms in intestinal wound repair. In conclusion, the enhanced release of TGF-β2 but reduced expression of TGF-β3 by Crohn's disease intestinal myofibroblasts, together with their enhanced proliferative capacity, may lead to the development of intestinal strictures.

Decreased concentrations of saccharase-isomaltase and villin in intestinal epithelial cells of Crohn's disease and ulcerative colitis

2000 ◽  
Vol 118 (4) ◽  
pp. A1118
Author(s):  
Matthias Bruewer ◽  
Klaus P. Zimmer ◽  
Axel Klotz ◽  
Sabine Kersting ◽  
Norbert Senninger ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Epithelial Cells ◽  
Intestinal Epithelial Cells ◽  
Intestinal Epithelial

Prebiotics and Probiotics in Inflammatory Bowel Disease: Where are we now and where are we going?

2020 ◽  
Vol 15 (3) ◽  
pp. 216-233 ◽  
Author(s):  
Maliha Naseer ◽  
Shiva Poola ◽  
Syed Ali ◽  
Sami Samiullah ◽  
Veysel Tahan
Keyword(s):  
Ulcerative Colitis ◽  
Inflammatory Bowel Disease ◽  
Clinical Trials ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Adverse Effects ◽  
Bowel Disease ◽  
Relapse Prevention ◽  
Remission Induction ◽  
Inflammatory Bowel

The incidence, prevalence, and cost of care associated with diagnosis and management of inflammatory bowel disease are on the rise. The role of gut microbiota in the causation of Crohn's disease and ulcerative colitis has not been established yet. Nevertheless, several animal models and human studies point towards the association. Targeting intestinal dysbiosis for remission induction, maintenance, and relapse prevention is an attractive treatment approach with minimal adverse effects. However, the data is still conflicting. The purpose of this article is to provide the most comprehensive and updated review on the utility of prebiotics and probiotics in the management of active Crohn’s disease and ulcerative colitis/pouchitis and their role in the remission induction, maintenance, and relapse prevention. A thorough literature review was performed on PubMed, Ovid Medline, and EMBASE using the terms “prebiotics AND ulcerative colitis”, “probiotics AND ulcerative colitis”, “prebiotics AND Crohn's disease”, “probiotics AND Crohn's disease”, “probiotics AND acute pouchitis”, “probiotics AND chronic pouchitis” and “prebiotics AND pouchitis”. Observational studies and clinical trials conducted on humans and published in the English language were included. A total of 71 clinical trials evaluating the utility of prebiotics and probiotics in the management of inflammatory bowel disease were reviewed and the findings were summarized. Most of these studies on probiotics evaluated lactobacillus, De Simone Formulation or Escherichia coli Nissle 1917 and there is some evidence supporting these agents for induction and maintenance of remission in ulcerative colitis and prevention of pouchitis relapse with minimal adverse effects. The efficacy of prebiotics such as fructooligosaccharides and Plantago ovata seeds in ulcerative colitis are inconclusive and the data regarding the utility of prebiotics in pouchitis is limited. The results of the clinical trials for remission induction and maintenance in active Crohn's disease or post-operative relapse with probiotics and prebiotics are inadequate and not very convincing. Prebiotics and probiotics are safe, effective and have great therapeutic potential. However, better designed clinical trials in the multicenter setting with a large sample and long duration of intervention are needed to identify the specific strain or combination of probiotics and prebiotics which will be more beneficial and effective in patients with inflammatory bowel disease.

scholarly journals The Changing Prognosis of Ulcerative Colitis and Crohn’s Disease by Decades

2021 ◽  
Author(s):  
Burton I Korelitz ◽  
Judy Schneider
Keyword(s):  
Ulcerative Colitis ◽  
Inflammatory Bowel Disease ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Medical Therapy ◽  
Bowel Disease ◽  
Surgical Intervention ◽  
Inflammatory Bowel

Abstract We present a bird’s eye view of the prognosis for both ulcerative colitis and Crohn’s disease as contained in the database of an Inflammatory Bowel Disease gastroenterologist covering the period from 1950 until the present utilizing the variables of medical therapy, surgical intervention, complications and deaths by decades.

scholarly journals Targeted 1H NMR metabolomics and immunological phenotyping of human fresh blood and serum samples discriminate between healthy individuals and inflammatory bowel disease patients treated with anti-TNF

2021 ◽  
Author(s):  
Sara Notararigo ◽  
Manuel Martín-Pastor ◽  
Juan E. Viñuela Roldán ◽  
Adriano Quiroga ◽  
J. Enrique Dominguez-Munoz ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Inflammatory Bowel Disease ◽  
Crohn’S Disease ◽  
Clinical Practice ◽  
Crohn's Disease ◽  
T Lymphocyte ◽  
Fresh Blood ◽  
Serum Samples ◽  
Nmr Metabolomics ◽  
Inflammatory Bowel

Abstract Inflammatory bowel disease is a multifactorial etiology, associated with environmental factors that can trigger both debut and relapses. A high level of tumor necrosis factor-α in the gut is the main consequence of immune system imbalance. The aim of treatment is to restore gut homeostasis. In this study, fresh blood and serum samples were used to identify biomarkers and to discriminate between Crohn’s disease and ulcerative colitis patients under remission treated with anti-TNF. Metabolomics based on Nuclear Magnetic Resonance spectroscopy (NMR) was used to detect unique biomarkers for each class of patients. Blood T lymphocyte repertories were characterized, as well as cytokine and transcription factor profiling, to complement the metabolomics data. Higher levels of homoserine-methionine and isobutyrate were identified as biomarkers of Crohn’s disease with ileocolic localization. For ulcerative colitis, lower levels of creatine-creatinine, proline, and tryptophan were found that reflect a deficit in the absorption of essential amino acids in the gut. T lymphocyte phenotyping and its functional profiling revealed that the overall inflammation was lower in Crohn’s disease patients than in those with ulcerative colitis. These results demonstrated that NMR metabolomics could be introduced as a high-throughput evaluation method in routine clinical practice to stratify both types of patients related to their pathology. Key messages NMR metabolomics is a non-invasive tool that could be implemented in the normal clinical practice for IBD to assess beneficial effect of the treatment. NMR metabolomics is a useful tool for precision medicine, in order to sew a specific treatment to a specific group of patients. Finding predictors of response to IFX would be desirable to select patients affected by IBD. Immunological status of inflammations correlates with NMR metabolomics biomarkers.

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 Inflammatory Bowel Disease: An Overview of Immune Mechanisms and Biological Treatments

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Bruno Rafael Ramos de Mattos ◽  
Maellin Pereira Gracindo Garcia ◽  
Julia Bier Nogueira ◽  
Lisiery Negrini Paiatto ◽  
Cassia Galdino Albuquerque ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Severe Disease ◽  
Biological Therapies ◽  
Promising Alternative ◽  
Biological Treatments ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
And Behavior

Inflammatory bowel diseases (IBD) are characterized by chronic inflammation of the intestinal tract associated with an imbalance of the intestinal microbiota. Crohn’s disease (CD) and ulcerative colitis (UC) are the most widely known types of IBD and have been the focus of attention due to their increasing incidence. Recent studies have pointed out genes associated with IBD susceptibility that, together with environment factors, may contribute to the outcome of the disease. In ulcerative colitis, there are several therapies available, depending on the stage of the disease. Aminosalicylates, corticosteroids, and cyclosporine are used to treat mild, moderate, and severe disease, respectively. In Crohn’s disease, drug choices are dependent on both location and behavior of the disease. Nowadays, advances in treatments for IBD have included biological therapies, based mainly on monoclonal antibodies or fusion proteins, such as anti-TNF drugs. Notwithstanding the high cost involved, these biological therapies show a high index of remission, enabling a significant reduction in cases of surgery and hospitalization. Furthermore, migration inhibitors and new cytokine blockers are also a promising alternative for treating patients with IBD. In this review, an analysis of literature data on biological treatments for IBD is approached, with the main focus on therapies based on emerging recombinant biomolecules.

scholarly journals PATIENTS WITH INFLAMMATORY BOWEL DISEASE PERSPECTIVE ON COVID-19 AND HEALTH CARE SERVICE DURING THE PANDEMIC

2021 ◽  
Vol 27 (Supplement_1) ◽  
pp. S50-S51
Author(s):  
Randi Opheim ◽  
Kristian Moum ◽  
Bjørn Moum
Keyword(s):  
Ulcerative Colitis ◽  
Health Care ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Medical Treatment ◽  
Biological Therapy ◽  
Care Service ◽  
Health Care Service ◽  
Inflammatory Bowel

Abstract Background Patients with inflammatory bowel diseases (IBD) have experienced changes to the routine management of their conditions during the coronavirus disease (COVID-19) pandemic. The disease as well IBD treatment frequently require immunosuppressant medications, which could increase their risk of infection. The aim of this study was to determine patients’ experience of the health care service, including the restrictions of hospitals visits made in Norway from Mars 12th 2020. Method From June 18 to September 18 2020, all patients at the IBD outpatient clinic at Oslo University Hospital in Norway on biological therapy or other immunosuppressant’s were included. A questionnaire including patients concerns regarding their disease, medical therapy and COVID-19, as well as their health care service needs in follow-up during the COVID-19 pandemic. Results Altogether 506 IBD patients answered a paper-based questionnaire. The mean age was 40.78 (SD 14.71), 289/506 (57%) men, ulcerative colitis 199/506 (39%), Crohn’s disease 307/506 (61%). Sixty-three patients (12.5%) used biological therapy in combination with azathioprine or steroids. Ninety-one (18.2%) were in obligated quarantine with negative test. Five patients (4.9%) tested positive to SARS- CoV-2 of the 98 patients tested, (1.0% of the total sample). One third of the IBD patients perceived they had increased risk for being infected by SARS- CoV-2 because of the immunosuppressive drugs they used. Nonetheless, 496/506 (98.6%) of the patients adhered to continuing their medication. One-hundred and sixty-one (32.3%) voluntarily isolated, and 21/506 (4.2%) was in sick leave being afraid of being infected. Furthermore, 20/506 (4.0%) cancelled their consultation because they were afraid of being infected from SARS- CoV-2 at the hospital. The hospital changed physical consultation to telephone consultation for 75/506 (15.0%) of the patients. Thirty-eight patients (7.6%) reported that they were afraid of going to the hospital because of restrictions due to the COVID-19 pandemic, and 18/506 (3.6%) did not feel safe when at hospital. Approximately half of the IBD patients (219/506) were satisfied with the information provided by physician about medical treatment for IBD and Covid-19 while 398/506 (77.3%) were satisfied with the information from health-care providers about restrictions due to COVID-19. There were no statistical differences between Crohn’s disease and ulcerative colitis. Conclusion IBD patients on biological treatment and immunosuppressives took precautions because of fear of being infected with SARS- CoV-2. At the same time, they adhere to medical treatment regimens and follow-up at the hospital. Most patients were satisfied with the information they received from physicians and other health-care workers. One percent tested positive to SARS-CoV-2.

Physiological Basis for Novel Drug Therapies Used to Treat the Inflammatory Bowel Diseases I. Immunology and therapeutic potential of antiadhesion molecule therapy in inflammatory bowel disease

2005 ◽  
Vol 288 (2) ◽  
pp. G169-G174 ◽  
Author(s):  
Gert Van Assche ◽  
Paul Rutgeerts
Keyword(s):  
Ulcerative Colitis ◽  
Inflammatory Bowel Disease ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Adhesion Molecules ◽  
Bowel Disease ◽  
Intestinal Inflammation ◽  
Therapeutic Potential ◽  
Physiological Basis ◽  
Inflammatory Bowel

Adhesion molecules regulate the influx of leukocytes in normal and inflamed gut. They are also involved in local lymphocyte stimulation and antigen presentation within the intestinal mucosa. In intestinal inflammation, many adhesion molecules are upregulated, but α4-integrins most likely hold a key position in directing leukocytes into the inflamed bowel wall. Therapeutic compounds directed against trafficking of leukocytes have been designed and are being developed as a novel class of drugs in the treatment of Crohn's disease and ulcerative colitis. This review deals with the immunological aspects of leukocyte trafficking focused on gut homing of T cells. Second, the changes in adhesion molecules and T cell trafficking during intestinal inflammation are discussed. Finally, we review the clinical data that have been gathered with respect to the therapeutic potential and the safety of antiadhesion molecule treatment. Antegren, or natalizumab, a humanized anti-α4 integrin IgG4 antibody, has been most extensively evaluated and may be close to registration. A more specific humanized α4β7-integrin MLN-02 has shown preliminary clinical efficacy in ulcerative colitis, and both antergren and MLN-02 appear to be very safe. Trials with the anti-ICAM-1 antisense oligonucleotide ISIS-2302 in steroid refractory Crohn's disease have provided conflicting efficacy data. In the near future, some of these novel biological agents may prove valuable therapeutic tools in the management of refractory inflammatory bowel disease, although it is too early to define the patient population that will benefit most from these agents.

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