scholarly journals Dichotomous roles of neutrophils in modulating pathogenic and repair processes of inflammatory bowel diseases

2021 ◽  
Author(s):  
Huimin Chen ◽  
Xiaohan Wu ◽  
Chunjin Xu ◽  
Jian Lin ◽  
Zhanju Liu
Keyword(s):  
Immune Cells ◽  
Inflammatory Bowel Diseases ◽  
Intestinal Inflammation ◽  
Critical Role ◽  
Mucosal Inflammation ◽  
Repair Processes ◽  
Microbial Invasion ◽  
Increased Risk ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Abstract Neutrophils are considered as complex innate immune cells and play a critical role in maintaining intestinal mucosal homeostasis. They exert robust pro-inflammatory effects and recruit other immune cells in the acute phase of pathogen infection and intestinal inflammation, but paradoxically, they also limit exogenous microbial invasion and facilitate mucosal restoration. Hyperactivation or dysfunction of neutrophils results in abnormal immune responses, leading to multiple autoimmune and inflammatory diseases including systemic lupus erythematosus, rheumatoid arthritis, and inflammatory bowel diseases (IBD). As a refractory intestinal inflammatory disease, the pathogenesis and progression of IBD are associated with complicated immune response processes in which neutrophils are profoundly involved. However, the consensus on potential roles of neutrophils in modulating pathogenic and repair processes of IBD remains not fully understood. Accumulated infiltrating neutrophils cross the epithelial barrier and contribute to microbial dysbiosis, aggravated intestinal architectural damage, compromised resolution of intestinal inflammation and increased risk of thrombosis during IBD. Paradoxically, activated neutrophils are also associated with effective elimination of invaded microbiota, promoted angiogenesis and tissue restoration of gut mucosa in IBD. Here, we discuss the beneficial and detrimental roles of neutrophils in the onset and resolution of intestinal mucosal inflammation and provide a precise overview of neutrophil functions in the pathogenesis of IBD.

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 Cell Death and Inflammatory Bowel Diseases: Apoptosis, Necrosis, and Autophagy in the Intestinal Epithelium

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Tiago Nunes ◽  
Claudio Bernardazzi ◽  
Heitor S. de Souza
Keyword(s):  
Cell Death ◽  
Inflammatory Bowel Diseases ◽  
Intestinal Inflammation ◽  
Critical Role ◽  
Receptor Activation ◽  
Tnf Receptor ◽  
Programmed Necrosis ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Cell Death Mechanisms

Cell death mechanisms have been associated with the development of inflammatory bowel diseases in humans and mice. Recent studies suggested that a complex crosstalk between autophagy/apoptosis, microbe sensing, and enhanced endoplasmic reticulum stress in the epithelium could play a critical role in these diseases. In addition, necroptosis, a relatively novel programmed necrosis-like pathway associated with TNF receptor activation, seems to be also present in the pathogenesis of Crohn’s disease and in specific animal models for intestinal inflammation. This review attempts to cover new data related to cell death mechanisms and inflammatory bowel diseases.

scholarly journals Effects of Boswellia serrata Roxb. and Curcuma longa L. in an In Vitro Intestinal Inflammation Model Using Immune Cells and Caco-2

2018 ◽  
Author(s):  
Paolo Governa ◽  
Maddalena Marchi ◽  
Veronica Cocetta ◽  
Bianca De Leo ◽  
Philippa T. K. Saunders ◽  
...  
Keyword(s):  
Mechanism Of Action ◽  
Immune Cells ◽  
Inflammatory Bowel Diseases ◽  
Intestinal Inflammation ◽  
Curcuma Longa ◽  
Intestinal Barrier Function ◽  
Boswellia Serrata ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Inflammatory bowel diseases, which consist of chronic inflammatory conditions of the colon and the small intestine, are considered a global disease of our modern society. Recently, the use of herbal therapies has increased in patients with inflammatory bowel diseases because of their effectiveness and better safety profile, compared to conventional drugs. Boswellia serrata Roxb. and Curcuma longa L. are amongst the most promising herbal drugs, however, their clinical use in inflammatory bowel diseases is limited and little is known on their mechanism of action. The aim of this work was to investigate the effects of two standardized extract of B. serrata and C. longa in an in vitro model of intestinal inflammation. Their impact on cytokine release and reactive oxygen species production, as well as the maintenance of the intestinal barrier function and on intestinal mucosa immune cells infiltration, has been evaluated. The extracts showed a good protective effect on the intestinal epithelium at 1 µg/ml, with C. longa having an anti-inflammatory mechanism of action and B. serrata acting as an antioxidant. In summary, these herbal products were demonstrated to be promising agents for the management of inflammatory bowel diseases by modulating in vitro parameters which have been identified in the clinical conditions.

scholarly journals A Dietary Cholesterol-Based Intestinal Inflammation Assay for Improving Drug-Discovery on Inflammatory Bowel Diseases

2021 ◽  
Vol 9 ◽  
Author(s):  
Nuno-Valério Silva ◽  
Diogo Carregosa ◽  
Catarina Gonçalves ◽  
Otília V. Vieira ◽  
Cláudia Nunes dos Santos ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Inflammatory Bowel Diseases ◽  
Intestinal Inflammation ◽  
Feeding Strategy ◽  
Critical Role ◽  
Dietary Cholesterol ◽  
High Cholesterol Diet ◽  
Transgenic Zebrafish ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Inflammatory bowel diseases (IBD) with chronic infiltration of immune cells in the gastrointestinal tract are common and largely incurable. The therapeutic targeting of IBD has been hampered by the complex causality of the disease, with environmental insults like cholesterol-enriched Western diets playing a critical role. To address this drug development challenge, we report an easy-to-handle dietary cholesterol-based in vivo assay that allows the screening of immune-modulatory therapeutics in transgenic zebrafish models. An improvement in the feeding strategy with high cholesterol diet (HCD) selectively induces a robust and consistent infiltration of myeloid cells in larvae intestines that is highly suitable for compound discovery efforts. Using transgenics with fluorescent reporter expression in neutrophils, we take advantage of the unique zebrafish larvae clarity to monitor an acute inflammatory response in a whole organism context with a fully functional innate immune system. The use of semi-automated image acquisition and processing combined with quantitative image analysis allows categorizing anti- or pro-inflammatory compounds based on a leukocytic inflammation index. Our HCD gut inflammation (HCD-GI) assay is simple, cost- and time-effective as well as highly physiological which makes it unique when compared to chemical-based zebrafish models of IBD. Besides, diet is a highly controlled, selective and targeted trigger of intestinal inflammation that avoids extra-intestinal outcomes and reduces the chances of chemical-induced toxicity during screenings. We show the validity of this assay for a screening platform by testing two dietary phenolic acids, namely gallic acid (GA; 3,4,5-trihydroxybenzoic acid) and ferulic acid (FA; 4-hydroxy-3-methoxycinnamic acid), with well described anti-inflammatory actions in animal models of IBD. Analysis of common IBD therapeutics (Prednisolone and Mesalamine) proved the fidelity of our IBD-like intestinal inflammation model. In conclusion, the HCD-GI assay can facilitate and accelerate drug discovery efforts on IBD, by identification of novel lead molecules with immune modulatory action on intestinal neutrophilic inflammation. This will serve as a jumping-off point for more profound analyses of drug mechanisms and pathways involved in early IBD immune responses.

Ultrasensitive molecular imaging of intestinal mucosal inflammation using leukocyte-mimicking particles targeted to MAdCAM-1 in mice

2020 ◽  
Vol 12 (560) ◽  
pp. eaaz4047
Author(s):  
Antoine P. Fournier ◽  
Sara Martinez de Lizarrondo ◽  
Adrien Rateau ◽  
Axel Gerard-Brisou ◽  
Maximilian J. Waldner ◽  
...  
Keyword(s):  
Adhesion Molecule ◽  
Intestinal Mucosa ◽  
Inflammatory Bowel Diseases ◽  
Intestinal Inflammation ◽  
Mucosal Inflammation ◽  
Molecular Mri ◽  
Mucosal Tissues ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Chronic Intestinal Inflammation

Mucosal tissues play critical roles in health and disease as the primary barrier between the external world and the inner body, lining the digestive, respiratory, urinary, mammary, and reproductive tracts. Clinical evaluation of mucosal tissues is currently performed using endoscopy, such as ileocolonoscopy for the intestinal mucosa, which causes substantial patient discomfort and can lead to organ damage. Here, we developed a contrast agent for molecular magnetic resonance imaging (MRI) that is targeted to mucosal vascular addressin cell adhesion molecule 1 (MAdCAM-1), an adhesion molecule overexpressed by inflamed mucosal tissues. We investigated the diagnostic performance of molecular MRI of MAdCAM-1 to detect mucosal inflammation in several models of acute and chronic intestinal inflammation in mice. We demonstrated that molecular MRI of MAdCAM-1 reveals disease activity and can evaluate the response to inflammatory treatments along the whole intestinal mucosa in clinically relevant models of inflammatory bowel diseases. We also provide evidence that this technique can detect low, subclinical mucosal inflammation. Molecular MRI of MAdCAM-1 has potential applications in early diagnosis, longitudinal follow-up, and therapeutic response monitoring in diseases affecting mucosal tissues, such as inflammatory bowel diseases.

scholarly journals Effects of Boswellia Serrata Roxb. and Curcuma longa L. in an In Vitro Intestinal Inflammation Model Using Immune Cells and Caco-2

2018 ◽  
Vol 11 (4) ◽  
pp. 126 ◽  
Author(s):  
Paolo Governa ◽  
Maddalena Marchi ◽  
Veronica Cocetta ◽  
Bianca De Leo ◽  
Philippa Saunders ◽  
...  
Keyword(s):  
Mechanism Of Action ◽  
Immune Cells ◽  
Inflammatory Bowel Diseases ◽  
Intestinal Inflammation ◽  
Curcuma Longa ◽  
Intestinal Barrier Function ◽  
Boswellia Serrata ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Inflammatory bowel diseases, which consist of chronic inflammatory conditions of the colon and the small intestine, are considered a global disease of our modern society. Recently, the interest toward the use of herbal therapies for the management of inflammatory bowel diseases has increased because of their effectiveness and favourable safety profile, compared to conventional drugs. Boswellia serrata Roxb. and Curcuma longa L. are amongst the most promising herbal drugs, however, their clinical use in inflammatory bowel diseases is limited and little is known on their mechanism of action. The aim of this work was to investigate the effects of two phytochemically characterized extracts of B. serrata and C. longa in an in vitro model of intestinal inflammation. Their impact on cytokine release and reactive oxygen species production, as well as the maintenance of the intestinal barrier function and on intestinal mucosa immune cells infiltration, has been evaluated. The extracts showed a good protective effect on the intestinal epithelium at 1 µg/mL, with TEER values increasing by approximately 1.5 fold, compared to LPS-stimulated cells. C. longa showed an anti-inflammatory mechanism of action, reducing IL-8, TNF-α and IL-6 production by approximately 30%, 25% and 40%, respectively, compared to the inflammatory stimuli. B. serrata action was linked to its antioxidant effect, with ROS production being reduced by 25%, compared to H2O2-stimulated Caco-2 cells. C. longa and B. serrata resulted to be promising agents for the management of inflammatory bowel diseases by modulating in vitro parameters which have been identified in the clinical conditions.

Neurological presentations of inflammatory bowel diseases

2021 ◽  
pp. 34-42
Author(s):  
Yu. O. Shulpekova ◽  
V. U. Ablaev ◽  
I. V. Damulin
Keyword(s):  
Inflammatory Bowel Diseases ◽  
Neurological Disorders ◽  
Intestinal Inflammation ◽  
Cranial Nerves ◽  
Cranial Neuropathy ◽  
Drug Induced ◽  
Axonal Polyneuropathy ◽  
Increased Risk ◽  
Bowel Diseases ◽  
Inflammatory Bowel

The aim. To characterize the main types of neurological manifestations in inflammatory bowel diseases – Crohn’s disease and ulcerative colitis.Main concepts. Neurological disorders represent an important aspect of extraintestinal inflammatory bowel diseases (IBD) manifestations. According to publications, the incidence of psycho-neurological syndromes varies from 0.25% to 47.50% that apparently depends on the patient’s selection in studies. Neurological signs are not always associated with IBD activity and may precede the manifestation of intestinal inflammation. The most typical include cerebral thromboembolism, peripheral and cranial neuropathies, demyelinating disorders, and cerebral vasculitis. The incidence of ischemic stroke in IBD can reach 6.4%, with approx. 20% of affected persons under 17 y.o. Hemiparesis is the predominant consequence. The risk of intracranial venous thrombosis is increased depending on the activity of intestinal inflammation; this complication can precede manifestation of IBD. Fifty per cent increased risk of multiple sclerosis in IBD patients was shown. The types of peripheral nerves involvement include mononeuropathy, plexopathy, multiple mononeuropathy, compression neuropathy, polyneuropathy and cranial neuropathy. Peripheral neuropathy may be found in 32–37% of IBD patients with a special examination. Demyelinating type, sensory axonal polyneuropathy with thin and thick fibers damage, and motor axonal polyneuropathy with thick fibers damage are observed approximately in equal proportions. It is important to differentiate ‘primary’ neuropathy with vitamin B12 and folic acid deficient, alcoholic, diabetic and drug-induced neuropathy. Clinical improvement is usually seen in the course of immunosuppressive therapy. Cranial neuropathy (mostly of II, VI, VII, VIII of cranial nerves) is described in IBD. Neurological disorders associated with administration of metronidazole, sulfasalazine, cyclosporin A, antibodies to TNF-α and integrins α4 and α4ß7 continue to be highly actual.Conclusion. There is a variety of neurologic syndromes in IBD which represents an important part of extraintestinal manifestations. Mild psychoneurological disorders may be not recognized in time. The majority of symptoms and signs may regress in the course of treatment of IBD and nutrients deficiency correction. The special attention should be paid to neurological status control while the biologic and immunosuppressor agents and metronidazole are administered.

scholarly journals The Role of Portal Vein Thrombosis in the Clinical Course of Inflammatory Bowel Diseases: Report on Three Cases and Review of the Literature

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Emanuele Sinagra ◽  
Emma Aragona ◽  
Claudia Romano ◽  
Simonetta Maisano ◽  
Ambrogio Orlando ◽  
...  
Keyword(s):  
Portal Vein ◽  
Portal Vein Thrombosis ◽  
Inflammatory Bowel Diseases ◽  
Vascular Complications ◽  
Hepatic Abscess ◽  
Vein Thrombosis ◽  
Increased Risk ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Thromboembolism Events

Inflammatory bowel diseases are associated with an increased risk of vascular complications. The most important are arterial and venous thromboembolisms, which are considered as specific extraintestinal manifestations of inflammatory bowel diseases. Among venous thromboembolism events, portal vein thrombosis has been described in inflammatory bowel diseases. We report three cases of portal vein thrombosis occurring in patients with active inflammatory bowel disease. In two of them, hepatic abscess was present. Furthermore, we performed a systematic review based on the clinical literature published on this topic.

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.

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