scholarly journals Cellular and molecular mediators of lymphangiogenesis in inflammatory bowel disease

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Dickson Kofi Wiredu Ocansey ◽  
Bing Pei ◽  
Xinwei Xu ◽  
Lu Zhang ◽  
Chinasa Valerie Olovo ◽  
...  
Keyword(s):  
Immune Cells ◽  
Molecular Mechanisms ◽  
Lymphatic System ◽  
Wide Spectrum ◽  
Adaptive Immune System ◽  
Therapeutic Interventions ◽  
Complex Processes ◽  
Inflammatory Conditions ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Abstract Background Recent studies reporting the intricate crosstalk between cellular and molecular mediators and the lymphatic endothelium in the development of inflammatory bowel diseases (IBD) suggest altered inflammatory cell drainage and lymphatic vasculature, implicating the lymphatic system as a player in the occurrence, development, and recurrence of intestinal diseases. This article aims to review recent data on the modulatory functions of cellular and molecular components of the IBD microenvironment on the lymphatic system, particularly lymphangiogenesis. It serves as a promising therapeutic target for IBD management and treatment. The interaction with gut microbiota is also explored. Main text Evidence shows that cells of the innate and adaptive immune system and certain non-immune cells participate in the complex processes of inflammatory-induced lymphangiogenesis through the secretion of a wide spectrum of molecular factors, which vary greatly among the various cells. Lymphangiogenesis enhances lymphatic fluid drainage, hence reduced infiltration of immunomodulatory cells and associated-inflammatory cytokines. Interestingly, some of the cellular mediators, including mast cells, neutrophils, basophils, monocytes, and lymphatic endothelial cells (LECs), are a source of lymphangiogenic molecules, and a target as they express specific receptors for lymphangiogenic factors. Conclusion The effective target of lymphangiogenesis is expected to provide novel therapeutic interventions for intestinal inflammatory conditions, including IBD, through both immune and non-immune cells and based on cellular and molecular mechanisms of lymphangiogenesis that facilitate inflammation resolution.

Gut Mycobiota and Fungal Metabolites in Human Homeostasis

2018 ◽  
Vol 20 (2) ◽  
pp. 232-240 ◽  
Author(s):  
Izabella Mogilnicka ◽  
Marcin Ufnal
Keyword(s):  
Wide Spectrum ◽  
Biological Effects ◽  
Fungal Species ◽  
Fungal Metabolites ◽  
Human Gut ◽  
Fecal Transplantation ◽  
Bacterial Microbiota ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Background:Accumulating evidence suggests that microbiota play an important role in host’s homeostasis. Thus far, researchers have mostly focused on the role of bacterial microbiota. However, human gut is a habitat for several fungal species, which produce numerous metabolites. Furthermore, various types of food and beverages are rich in a wide spectrum of fungi and their metabolites.Methods:We searched PUBMED and Google Scholar databases to identify clinical and pre-clinical studies on fungal metabolites, composition of human mycobiota and fungal dysbiosis.Results:Fungal metabolites may serve as signaling molecules and exert significant biological effects including trophic, anti-inflammatory or antibacterial actions. Finally, research suggests an association between shifts in gut fungi composition and human health. Changes in mycobiota composition have been found in obesity, hepatitis and inflammatory bowel diseases.Conclusion:The influence of mycobiota and dietary fungi on homeostasis in mammals suggests a pharmacotherapeutic potential of modulating the mycobiota which may include treatment with probiotics and fecal transplantation. Furthermore, antibacterial action of fungi-derived molecules may be considered as a substitution for currently used antibacterial agents and preservatives in food industry.

scholarly journals Loss of Nckx3 Exacerbates Experimental DSS-Induced Colitis in Mice through p53/NF-κB Pathway

2021 ◽  
Vol 22 (5) ◽  
pp. 2645
Author(s):  
Dinh Nam Tran ◽  
Seon Myeong Go ◽  
Seon-Mi Park ◽  
Eui-Man Jung ◽  
Eui-Bae Jeung
Keyword(s):  
Immune Response ◽  
Cellular Proliferation ◽  
Intestinal Inflammation ◽  
Critical Role ◽  
Experimental Colitis ◽  
Innate Immune ◽  
Inflammatory Conditions ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Microarray Analyses

Inflammatory bowel diseases (IBDs) comprises a range of chronic inflammatory conditions of the intestinal tract. The incidence and prevalence of IBDs are increasing worldwide, but the precise etiology of these diseases is not completely understood. Calcium signaling plays a regulatory role in cellular proliferation. Nckx3, a potassium-dependent Na+/Ca2+ exchanger, is not only expressed in the brain but also in the aortic, uterine, and intestinal tissues, which contain abundant smooth muscle cells. This study investigated the role of Nckx3 in intestinal inflammation. Microarray analyses revealed the upregulation of the innate immune response-associated genes in the duodenum of Nckx3 knockout (KO) mice. The Nckx3 KO mice also showed an increase in IBD- and tumorigenesis-related genes. Using dextran sodium sulfate (DSS)-induced experimental colitis mice models, the Nckx3 KO mice showed severe colitis. Furthermore, the pathways involving p53 and NF-κB signaling were significantly upregulated by the absence of Nckx3. Overall, Nckx3 plays a critical role in the innate immune and immune response and may be central to the pathogenesis of IBD.

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 Clinical assessment of inflammatory bowel disease activity: a critical overview

2015 ◽  
Vol 84 (2) ◽  
pp. 113-125
Author(s):  
Adam Fabisiak ◽  
Natalia Murawska ◽  
Anna Mokrowiecka ◽  
Ewa Małecka-Panas ◽  
Jakub Fichna
Keyword(s):  
Ulcerative Colitis ◽  
Inflammatory Bowel Disease ◽  
Clinical Aspects ◽  
Gi Tract ◽  
Inflammatory Conditions ◽  
Symptom Recognition ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Critical Overview ◽  
Future Concepts

Crohn’s disease (CD) and ulcerative colitis (UC), which belong to the group of inflammatory bowel diseases (IBD), are chronic inflammatory conditions of the gastrointestinal (GI) tract. Over the last eighty years the overview of IBD has evolved, along with disease symptom recognition, hypotheses on etiology and recommendations for clinical treatment. This review focuses on the clinical aspects of IBD throughout the years and discusses the most recent and future concepts in IBD diagnosis.

scholarly journals Immunological Mechanisms in Inflammation-Associated Colon Carcinogenesis

2020 ◽  
Vol 21 (9) ◽  
pp. 3062 ◽  
Author(s):  
Takehiro Hirano ◽  
Daisuke Hirayama ◽  
Kohei Wagatsuma ◽  
Tsukasa Yamakawa ◽  
Yoshihiro Yokoyama ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Molecular Mechanisms ◽  
T Helper 17 ◽  
Colon Inflammation ◽  
Immunological Mechanisms ◽  
Increased Risk ◽  
Bowel Diseases ◽  
Cumulative Rate ◽  
T Helper 17 Cell ◽  
Inflammatory Bowel

Patients with chronic inflammatory bowel diseases are at an increased risk of developing colitis-associated cancer (CAC). Chronic inflammation positively correlates with tumorigenesis. Similarly, the cumulative rate of incidence of developing CAC increases with prolonged colon inflammation. Immune signaling pathways, such as nuclear factor (NF)-κB, prostaglandin E2 (PGE2)/cyclooxygenase-2 (COX-2), interleukin (IL)-6/signal transducer and activator of transcription 3 (STAT3), and IL-23/T helper 17 cell (Th17), have been shown to promote CAC tumorigenesis. In addition, gut microbiota contributes to the development and progression of CAC. This review summarizes the signaling pathways involved in the pathogenesis following colon inflammation to understand the underlying molecular mechanisms in CAC tumorigenesis.

scholarly journals Microbiota-independent immunological effects of non-digestible oligosaccharides in the context of inflammatory bowel diseases

2020 ◽  
Vol 79 (4) ◽  
pp. 468-478 ◽  
Author(s):  
Stefania Del Fabbro ◽  
Philip C. Calder ◽  
Caroline E. Childs
Keyword(s):  
Inflammatory Bowel Diseases ◽  
Immune Cell ◽  
Intestinal Inflammation ◽  
Mechanisms Of Action ◽  
Mucosal Inflammation ◽  
Disease States ◽  
Inflammatory Conditions ◽  
Bowel Diseases ◽  
Inflammatory Bowel

The aim of the present paper is to review the effects of non-digestible oligosaccharides (NDO) on immunity, focusing on their microbiota-independent mechanisms of action, as well as to explore their potential beneficial role in inflammatory bowel diseases (IBD). IBD are chronic, inflammatory conditions of the gastrointestinal tract. Individuals with IBD have an aberrant immune response to commensal microbiota, resulting in extensive mucosal inflammation and increased intestinal permeability. NDO are prebiotic fibres well known for their role in supporting intestinal health through modulation of the gut microbiota. NDO reach the colon intact and are fermented by commensal bacteria, resulting in the production of SCFA with immunomodulatory properties. In disease states characterised by increased gut permeability, prebiotics may also bypass the gut barrier and directly interact with intestinal and systemic immune cells, as demonstrated in patients with IBD and in infants with an immature gut. In vitro models show that fructooligosaccharides, inulin and galactooligosaccharides exert microbiota-independent effects on immunity by binding to toll-like receptors on monocytes, macrophages and intestinal epithelial cells and by modulating cytokine production and immune cell maturation. Moreover, animal models and human supplementation studies demonstrate that some prebiotics, including inulin and lactulose, might reduce intestinal inflammation and IBD symptoms. Although there are convincing preliminary data to support NDO as immunomodulators in the management of IBD, their mechanisms of action are still unclear and larger standardised studies need to be performed using a wider range of prebiotics.

scholarly journals The Immunological Basis of Inflammatory Bowel Disease

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Francesca A. R. Silva ◽  
Bruno L. Rodrigues ◽  
Maria de Lourdes S. Ayrizono ◽  
Raquel F. Leal
Keyword(s):  
Th17 Cells ◽  
Inflammatory Process ◽  
Adaptive Immune System ◽  
Treg Cells ◽  
Intestinal Wall ◽  
Adaptive Immune ◽  
Current State ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Inflammatory Profile

Inflammatory bowel diseases (IBDs) are chronic ailments, Crohn’s disease and ulcerative colitis being the most important. These diseases present an inflammatory profile and they differ according to pathophysiology, the affected area in the gastrointestinal tract, and the depth of the inflammation in the intestinal wall. The immune characteristics of IBD arise from abnormal responses of the innate and adaptive immune system. The number of Th17 cells increases in the peripheral blood of IBD patients, while Treg cells decrease, suggesting that the Th17/Treg proportion plays an important role in the development and maintenance of inflammation. The purpose of this review was to determine the current state of knowledge on the immunological basis of IBD. Many studies have shown the need for further explanation of the development and maintenance of the inflammatory process.

scholarly journals P301 Agreement in histologic diagnosis of preneoplastic lesions in inflammatory bowel disease: Results from a national survey in Italy

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S303-S304
Author(s):  
G Canavese ◽  
L Saragoni ◽  
T Salviato ◽  
L Reggiani Bonetti ◽  
G Leoncini ◽  
...  
Keyword(s):  
Comprehensive Evaluation ◽  
Disease Classification ◽  
Preneoplastic Lesions ◽  
Histologic Diagnosis ◽  
Surgical Specimen ◽  
Inflammatory Conditions ◽  
Learning Platform ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Good Agreement

Abstract Background Inflammatory bowel diseases (IBD) are chronic inflammatory conditions of gastrointestinal tract: the inflammatory damage increases the risk of developing preneoplastic and neoplastic conditions. Therefore, a good agreement between pathologists in the detection of preneoplastic lesion is essential in the management of IBD patients, in order to decrease the risk of progression towards neoplastic lesions. An agreement study on 4 pathologists and 38 cases of dysplasia demonstrated a fair agreement (k=0.4).1 A similar study demonstrated that the lowest level of agreement in the category indefinite for dysplasia (κ = 0.251). Methods The study consisted of a survey about diagnostic agreement in a series of preneoplastic lesions of IBD-affected patients, based on digital images. The occurrence of the disease and the occurrence of dysplasia were considered in the study. The study enclosed biopsy specimens from 30 colonoscopies and 1 surgical specimen, related to 20 patients with a clinical pattern of IBD from 4 reference centres in Italy. Digital slides were uploaded in an open-source learning platform. For each endoscopy, sampling sites with similar morphology were aggregated in 54 ‘blocks’, and a series of close-ended questions about (A) the occurrence of IBD (active, in remission, absent, not evaluable) and (B) the evidence of dysplasia (LG, HG, absent, undefined) have been submitted for every block. For each case, a final comprehensive evaluation about (1) the occurrence of IBD (present, absent, unsuitable for assessment), (2) the disease classification (ulcerative colitis, Crohn’s disease, unfit for differential diagnosis, not possible for lack of clinical data), (3) the occurrence of IBD-related dysplasia (IBD with dysplasia, dysplasia not IBD-related, dysplasia untestable, absent) and (4) the classification of dysplasia (sporadic adenoma, ALM, DALM, unclassifiable) were provided. Twenty gastrointestinal pathologists from as many centres in Italy were enrolled. Results 325 of the 400 tests were successfully concluded. Agreement values Conclusion A preliminary data analysis demonstrated a good agreement about the occurrence of IBD, and a lower agreement about the occurrence of dysplasia and its classification in IBD. Analysis of the correlation between agreement and clinical-histologic parameters could provide interesting spotlights on diagnostic algorithms in this field.

scholarly journals Role of Th17 Cells in the Pathogenesis of Human IBD

2014 ◽  
Vol 2014 ◽  
pp. 1-14 ◽  
Author(s):  
Julio Gálvez
Keyword(s):  
Th17 Cells ◽  
Current Knowledge ◽  
Th2 Cells ◽  
Th1 Cells ◽  
Inflammatory Conditions ◽  
Normal Microbiota ◽  
Bowel Diseases ◽  
Mucosal Homeostasis ◽  
Inflammatory Bowel

The gastrointestinal tract plays a central role in immune system, being able to mount efficient immune responses against pathogens, keeping the homeostasis of the human gut. However, conditions like Crohn’s disease (CD) or ulcerative colitis (UC), the main forms of inflammatory bowel diseases (IBD), are related to an excessive and uncontrolled immune response against normal microbiota, through the activation of CD4+ T helper (Th) cells. Classically, IBD was thought to be primarily mediated by Th1 cells in CD or Th2 cells in UC, but it is now known that Th17 cells and their related cytokines are crucial mediators in both conditions. Th17 cells massively infiltrate the inflamed intestine of IBD patients, where they produce interleukin- (IL-) 17A and other cytokines, triggering and amplifying the inflammatory process. However, these cells show functional plasticity, and they can be converted into either IFN-γ producing Th1 cells or regulatory T cells. This review will summarize the current knowledge regarding the regulation and functional role of Th17 cells in the gut. Deeper insights into their plasticity in inflammatory conditions will contribute to advancing our understanding of the mechanisms that regulate mucosal homeostasis and inflammation in the gut, promoting the design of novel therapeutic approaches for IBD.

scholarly journals Optimizing biologic therapy in inflammatory bowel disease: a Delphi consensus in the United Arab Emirates

2021 ◽  
Vol 14 ◽  
pp. 175628482110653
Author(s):  
Vito Annese ◽  
Rahul Nathwani ◽  
Maryam Alkhatry ◽  
Ahmad Al-Rifai ◽  
Sameer Al Awadhi ◽  
...  
Keyword(s):  
United Arab Emirates ◽  
Biologic Therapy ◽  
Negative Impact ◽  
Significant Proportion ◽  
Work Productivity ◽  
Delphi Consensus ◽  
Inflammatory Conditions ◽  
Bowel Diseases ◽  
Related Quality ◽  
Inflammatory Bowel

Background: Inflammatory bowel diseases (IBD) are chronic, relapsing-remitting inflammatory conditions with a substantial negative impact on health-related quality of life and work productivity. Treatment of IBD has been revolutionized by the advent of biologic therapies, initially with anti-TNF agents and more recently with multiple alternatives targets, and yet more under development. Objectives: Approximatively one third of patients do not respond to biologic therapy and more importantly a significant proportion experiences partial response or loss of response during treatment. The latter are common clinical situations and paradoxically are not addressed in the commercial drug labels and available guidelines. There is therefore a clinical need for physicians to understand when and how eventually to optimize the biologic therapy. Design: This consensus using a Delphi methodology was promoted and supported by the Emirates Society of Gastroenterology and Hepatology to close this gap. Data Sources and Methods: Following an extensive systematic review of over 60,000 studies, 81 studies with dose escalation and five addressing drug monitoring were selected and in addition five systematic reviews and three guidelines. Results and Conclusion: after three rounds of voting 18 statements were selected with agreement ranging from of 80% to 100%

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