scholarly journals Immunotherapeutic Effects of β-D Mannuronic Acid on IL-4, GATA3, IL-17 and RORC Gene Expression in the PBMC of Patients with Inflammatory Bowel Diseases

2018 ◽  
Author(s):  
Hussaini Alhassan Mohammed ◽  
Ali Akbar Saboor-Yaraghi ◽  
Homayoun Vahedi ◽  
Ghordratollah Panahi ◽  
Gholamreza Hemmasi ◽  
...  
Keyword(s):  
Inflammatory Bowel Diseases ◽  
Immunological Response ◽  
Quantitative Real Time Pcr ◽  
Mannuronic Acid ◽  
Immune Mediated ◽  
Genes Expression ◽  
Bowel Diseases ◽  
Research Findings ◽  
Inflammatory Bowel ◽  
Normal Controls

Inflammatory bowel diseases (IBD) are chronic relapsing immune-mediated disorders that result from an aberrant immunological response. IBD comprises of Crohn's disease (CD) and ulcerative colitis (UC). The precise aetiology of IBD has not been fully understood, however, recent studies support the hypothesis that patients with IBD have a dysregulated immune response to endogenous bacteria in the gastrointestinal tract (GIT). The increasing number of hospitalisation coupled with the high economic burden faced by IBD patients, calls for more concerted research efforts, to design a potent and credible treatment option for these strata of patients. This research was designed to test the efficacy and potency of β-D Mannuronic acid (M2000) in the treatment of IBD. Ten ml of blood was aseptically collected from 24 IBD patients and 24 normal controls. PBMC was isolated and stimulated with 1 µg/mL of LPS and incubated for 4 hours. The cells were later treated with 10 µg/mL or 50 µg/mL of Mannuronic acid and incubated for 24 hours at 370C under 5% CO2 and 100% humidity. After the incubation, RNA was extracted from the cells, cDNA was synthesised, and the expression of the gene was evaluated using quantitative real-time PCR. The result indicated a significant down-regulation of RORC and IL-17 genes expression, while the expression of IL-4 and GATA3 genes were significantly up-regulated. These research findings have shown that M2000 a biocompatible agent, that has an immunotherapeutic, immunomodulatory and immunosuppressive effects on the PBMC of IBD patients.

scholarly journals Procoagulatory State in Inflammatory Bowel Diseases Is Promoted by Impaired Intestinal Barrier Function

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Luca Pastorelli ◽  
Elena Dozio ◽  
Laura Francesca Pisani ◽  
Massimo Boscolo-Anzoletti ◽  
Elena Vianello ◽  
...  
Keyword(s):  
Inflammatory Bowel Diseases ◽  
Intestinal Barrier ◽  
Systemic Circulation ◽  
Intestinal Barrier Function ◽  
Inflammatory Conditions ◽  
Immune Mediated ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Molecular Patterns ◽  
D Dimer

Inflammatory and immune mediated disorders are risk factors for arterial and venous thromboembolism. Inflammatory bowel diseases (IBD) confer an even greater risk of thromboembolic events than other inflammatory conditions. It has been shown that IBD patients display defective intestinal barrier functions. Thus, pathogen-associated molecular patterns (PAMPs) coming from the intestinal bacterial burden might reach systemic circulation and activate innate immunity receptors on endothelial cells and platelets, promoting a procoagulative state. Aim of the study was to test this hypothesis, correlating the presence of circulating PAMPs with the activation of innate immune system and the activation of the coagulatory cascade in IBD patients. Specifically, we studied lipopolysaccharide (LPS), Toll-like receptor (TLR) 2, TLR4, and markers of activated coagulation (i.e., D-Dimer and prothrombin fragmentF1+2) in the serum and plasma of IBD patients. We found that LPS levels are increased in IBD and correlate with TLR4 concentrations; although a mild correlation between LPS and CRP levels was detected, clinical disease activity does not appear to influence circulating LPS. Instead, serum LPS correlates with both D-Dimer andF1+2measurements. Taken together, our data support the role of an impairment of intestinal barrier in triggering the activation of the coagulatory cascade in IBD.

scholarly journals Evidence for a Potential Role of Metallothioneins in Inflammatory Bowel Diseases

2009 ◽  
Vol 2009 ◽  
pp. 1-9 ◽  
Author(s):  
Anouk Waeytens ◽  
Martine De Vos ◽  
Debby Laukens
Keyword(s):  
Inflammatory Bowel Diseases ◽  
Potential Role ◽  
Current Knowledge ◽  
Zinc Homeostasis ◽  
Central Position ◽  
Small Proteins ◽  
Immune Mediated ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Inflammatory bowel diseases (IBDs) are a group of chronic, relapsing, immune-mediated disorders of the intestine, including Crohn's disease and ulcerative colitis. Recent studies underscore the importance of the damaged epithelial barrier and the dysregulated innate immune system in their pathogenesis. Metallothioneins (MTs) are a family of small proteins with a high and conserved cysteine content that are rapidly upregulated in response to an inflammatory stimulus. Herein, we review the current knowledge regarding the expression and potential role of MTs in IBD. MTs exert a central position in zinc homeostasis, modulate the activation of the transcription factor nuclear factor (NF)-B, and serve as antioxidants. In addition, MTs could be involved in IBD through their antiapoptotic effects or through specific immunomodulating extracellular effects. Reports on MT expression in IBD are contradictory but clearly demonstrate a deviant MT expression supporting the idea that these aberrations in IBD require further clarification.

scholarly journals Frailty in inflammatory bowel diseases: an emerging concept

2021 ◽  
Vol 14 ◽  
pp. 175628482110254
Author(s):  
Bharati Kochar ◽  
Ariela R. Orkaby ◽  
Ashwin N. Ananthakrishnan ◽  
Christine S. Ritchie
Keyword(s):  
Older Adults ◽  
Inflammatory Bowel Diseases ◽  
Conceptual Models ◽  
Younger Adults ◽  
Inflammatory Conditions ◽  
Immune Mediated ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
The Relationship ◽  
Improve Health

Inflammatory bowel diseases (IBD), consisting of Crohn’s disease and ulcerative colitis, are chronic remitting, relapsing inflammatory conditions of the gastrointestinal tract. While traditionally a disease of younger ages, the number of older adults with IBD is rising rapidly. Patients with IBD often experience geriatric syndromes at earlier ages. Older adults with IBD have poorer disease and treatment-related outcomes compared with younger adults with IBD. Applying the principles of geriatrics to understanding a chronic disease in older adults may improve health span. Better tools are needed to stratify IBD patients who are at high risk for adverse events. Frailty is a geriatric construct that may approximate biologic age. Frailty is a complex, multi-dimensional syndrome that leads to increased vulnerability to stress and decline of reserve across multiple physiologic systems. In this review, we present the leading conceptual models of frailty and discuss the applications of frailty in immune-mediated diseases. We also review chronic conditions where frailty has been applied successfully as a tool for risk stratification. Finally, we discuss in the detail the growing body of literature highlighting the relationship between frailty and IBD, the epidemiology of frailty in IBD, and ramifications of frailty in IBD.

scholarly journals P795 Risk of incident paradoxical immune-mediated inflammatory diseases in patients with inflammatory bowel diseases treated with anti-TNF therapies: a nationwide Danish cohort study

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S625-S625
Author(s):  
D WARD ◽  
S Gørtz ◽  
N Nyboe Andersen ◽  
J Kirchgesner ◽  
T Jess
Keyword(s):  
Rheumatoid Arthritis ◽  
Cohort Study ◽  
Inflammatory Bowel Diseases ◽  
Hidradenitis Suppurativa ◽  
Inflammatory Diseases ◽  
Hazard Ratios ◽  
Immune Mediated ◽  
Bowel Diseases ◽  
Lag Period ◽  
Inflammatory Bowel

Abstract Background Tumour necrosis factor (TNF) has a central role in the pathophysiology of immune-mediated inflammatory diseases (IMIDs) including rheumatoid arthritis, psoriasis, hidradenitis suppurativa, and inflammatory bowel diseases (IBD). However, there have been case reports of patients receiving an anti-TNF therapy for one IMID subsequently developing a second IMID. We conducted a nationwide cohort study investigating the risk of incident IMID following anti-TNF exposure in patients with IBD in Denmark. Methods We followed patients with IBD from 1 January 2005 or date of IBD diagnosis (whichever occurred last) to an outcome event including incident diagnosis of hidradenitis suppurativa, arthropathic psoriasis, other forms of psoriasis, or rheumatoid arthritis; or emigration, death or 31 December 2018 (whichever occurred first). Patients were defined as exposed after a 3-month lag period from first anti-TNF infusion throughout follow-up, analogous to an intention-to-treat design. The lag period was censored from analyses to avoid including incipient IMIDs, unlikely to be caused by newly initiated anti-TNF treatment. We excluded patients initiating anti-TNF or with an outcome diagnosis before either 1 January 2005 or IBD diagnosis. We used Cox regression models with age as the underlying timescale, and sex, type of IBD (Crohn’s disease or ulcerative colitis), and calendar period of IBD diagnosis (in 5 year groups) as strata to estimate hazard ratios for each outcome, comparing anti-TNF users and non-users. Results Incidence rates (and 95% confidence intervals [CI]) as events per 100 000 person-years among anti-TNF users and non-users were, respectively, 138 (109–173) and 25.6 (22.0–29.7) for hidradenitis suppurativa, 26.3 (15.6–44.4) and 7.81 (5.95–10.2) for arthropathic psoriasis, 1177 (1085–1277) and 204 (121–189) for other forms of psoriasis, and 152 (121–189) and 95.6 (88.5–103) for rheumatoid arthritis. Hazard ratios (and 95% C.I.) were increased for hidradenitis suppurativa 2.91 (2.15–3.94), arthropathic psoriasis 2.62 (1.40–4.93), other forms of psoriasis 4.76 (4.27–5.31), and rheumatoid arthritis 2.35 (1.83–3.01). Conclusion The results indicate that patients with IBD receiving anti-TNF have an increased risk of IMIDs. An almost 5-fold increase in the risk of psoriasis is consistent with previous reports of psoriasiform skin lesions related to anti-TNF use. However, as more severe IBD is likely to be associated with both initiating anti-TNF and the incidence of other inflammatory diseases, the results are subject to confounding by indication. Thus, these results should be considered preliminary, and we plan to further address confounding by using propensity score methods.

scholarly journals TOFACITINIB IN THE MANAGEMENT OF ULCERATIVE COLITIS REFRACTORY TO ANTI-TNF AND ANTI-INTEGRIN THERAPIES

2018 ◽  
Vol 55 (2) ◽  
pp. 198-200 ◽  
Author(s):  
Fábio Vieira TEIXEIRA ◽  
Adérson Omar Mourão Cintra DAMIÃO ◽  
Paulo Gustavo KOTZE
Keyword(s):  
Ulcerative Colitis ◽  
Mechanism Of Action ◽  
Inflammatory Bowel Diseases ◽  
Lymphocyte Activation ◽  
Activation Function ◽  
Janus Kinases ◽  
Immune Mediated ◽  
Endoscopic Remission ◽  
Bowel Diseases ◽  
Inflammatory Bowel

ABSTRACT Janus kinases inhibitors have already been incorporated into the management of immune-mediated diseases, such as rheumatoid arthritis, and are being investigated for the treatment of psoriasis and inflammatory bowel diseases, both ulcerative colitis and Crohn’s disease. Tofacitinib is an oral small-molecule drug that inhibits Janus kinases 1, Janus kinases 3, and, to a lesser extent, Janus kinases 2. This inhibition ends up blocking signals for several inflammatory cytokines that are involved in the pathogenesis of inflammatory bowel diseases and play a role in many immune signaling routes, including lymphocyte activation, function, and proliferation. We report a patient with active ulcerative colitis with primary non-response to three biologics (infliximab, adalimumab and vedolizumab), with different mechanisms of action, who refused surgical treatment and had a favorable response to tofacitinib with clinical and endoscopic remission. No adverse events were observed with the use of the agent. This case illustrates the difficulties we may face regarding the identification of the expression of proper mechanism of action involved in the pathogenesis of ulcerative colitis patients and the importance of having another treatment option with different mechanism of action, like tofacitinib.

scholarly journals The Role of Extracellular Matrix Components in Inflammatory Bowel Diseases

2021 ◽  
Vol 10 (5) ◽  
pp. 1122
Author(s):  
Alicja Derkacz ◽  
Paweł Olczyk ◽  
Krystyna Olczyk ◽  
Katarzyna Komosinska-Vassev
Keyword(s):  
Extracellular Matrix ◽  
Inflammatory Bowel Diseases ◽  
Healing Process ◽  
Immunological Response ◽  
Matrix Remodeling ◽  
Ecm Remodeling ◽  
Intestinal Fibrosis ◽  
Extracellular Matrix Components ◽  
Bowel Diseases ◽  
Inflammatory Bowel

The remodeling of extracellular matrix (ECM) within the intestine tissues, which simultaneously involves an increased degradation of ECM components and excessive intestinal fibrosis, is a defining trait of the progression of inflammatory bowel diseases (IBDs), which include ulcerative colitis (UC) and Crohn’s disease (CD). The increased activity of proteases, especially matrix metalloproteinases (MMPs), leads to excessive degradation of the extracellular matrix and the release of protein and glycoprotein fragments, previously joined with the extracellular matrix, into the circulation. MMPs participate in regulating the functions of the epithelial barrier, the immunological response, and the process of wound healing or intestinal fibrosis. At a later stage of fibrosis during IBD, excessive formation and deposition of the matrix is observed. To assess changes in the extracellular matrix, quantitative measurement of the concentration in the blood of markers dependent on the activity of proteases, involved in the breakdown of extracellular matrix proteins as well as markers indicating the formation of a new ECM, has recently been proposed. This paper describes attempts to use the quantification of ECM components as markers to predict intestinal fibrosis and evaluate the healing process of the gut. The markers which reflect increased ECM degradation, together with the ones which show the process of creating a new matrix during IBD, allow the attainment of important information regarding the changes in the intestinal tissue, epithelial integrity and extracellular matrix remodeling. This paper contains evidence confirming that ECM remodeling is an integral part of directional cell signaling in the progression of IBD, and not only a basis for the ongoing processes.

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