The role of the intestinal microvasculature in inflammatory bowel disease: studies with a modified Caco-2 model including endothelial cells resembling the intestinal barrier in vitro

Intestinal Microbiota ◽

Bowel Disease ◽

Intestinal Barrier ◽

Innate Immune ◽

Intestinal Barrier Function ◽

Innate Immune Responses ◽

Susceptible Host ◽

A significant overlap exists between spondyloarthritis (SpA) and inflammatory bowel disease (IBD), particularly in the IL-23/IL-17 pathway. Shared immunologic mechanisms include aberrant innate immune responses, an excess of Th1/Th17-mediated immunity, and inadequate immune regulation. Many genetic factors associated with IBD are involved in host–pathogen interactions and intestinal barrier function, and the intestinal microbiota do appear to play an important role in disease development. Hence the current hypothesis for IBD pathogenesis is that it stems from a dysregulated immune response to intestinal microbiota in a genetically susceptible host. In SpA, evidence for a role of intestinal microbiota is less abundant, but given the overlap with IBD, it is plausible that gut microbiota are important players in SpA pathogenesis as well. However, there are significant genetic differences between these two conditions, as well as differing responses to biologic therapy.

S889 Effects of Etoh on Human Intestinal Epithelial and Microvascular Endothelial Cells (HIMEC) in Patients With Inflammatory Bowel Disease: An in-vitro Exploration

The American Journal of Gastroenterology ◽

10.14309/01.ajg.0000777088.45229.0e ◽

2021 ◽

Vol 116 (1) ◽

pp. S418-S418

Author(s):

Mohamed Tausif Siddiqui ◽

Gail West ◽

Gail Cresci

Keyword(s):

Endothelial Cells ◽

Bowel Disease ◽

Microvascular Endothelial Cells ◽

Intestinal Epithelial ◽

Inflammatory Bowel ◽

Microvascular Endothelial

Immunomodulatory role of Parkinson’s disease 7 in inflammatory bowel disease

Scientific Reports ◽

10.1038/s41598-021-93671-1 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Rita Lippai ◽

Apor Veres-Székely ◽

Erna Sziksz ◽

Yoichiro Iwakura ◽

Domonkos Pap ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Bowel Disease ◽

Intestinal Inflammation ◽

Tnf Α ◽

Inflammatory Bowel ◽

Ht 29

AbstractRecently the role of Parkinson’s disease 7 (PARK7) was studied in gastrointestinal diseases, however, the complex role of PARK7 in the intestinal inflammation is still not completely clear. Expression and localization of PARK7 were determined in the colon biopsies of children with inflammatory bowel disease (IBD), in the colon of dextran sodium sulphate (DSS) treated mice and in HT-29 colonic epithelial cells treated with interleukin (IL)-17, hydrogen peroxide (H2O2), tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β or lipopolysaccharide (LPS). Effect of PARK7 on the synthesis of IBD related cytokines was determined using PARK7 gene silenced HT-29 cells and 3,4,5-trimethoxy-N-(4-(8-methylimidazo(1,2-a)pyridine-2-yl)phenyl)benzamide (Comp23)—compound increasing PARK7 activity—treated mice with DSS-colitis. PARK7 expression was higher in the mucosa of children with Crohn’s disease compared to that of controls. While H2O2 and IL-17 treatment increased, LPS, TNF-α or TGF-β treatment decreased the PARK7 synthesis of HT-29 cells. PARK7 gene silencing influenced the synthesis of IL1B, IL6, TNFA and TGFB1 in vitro. Comp23 treatment attenuated the ex vivo permeability of colonic sacs, the clinical symptoms, and mucosal expression of Tgfb1, Il1b, Il6 and Il10 of DSS-treated mice. Our study revealed the role of PARK7 in the regulation of IBD-related inflammation in vitro and in vivo, suggesting its importance as a future therapeutic target.

Divergent Effect of Cigarette Smoke on Innate Immunity in Inflammatory Bowel Disease: A Nicotine-Infection Interaction

International Journal of Molecular Sciences ◽

10.3390/ijms21165801 ◽

2020 ◽

Vol 21 (16) ◽

pp. 5801 ◽

Cited By ~ 2

Author(s):

Dania AlQasrawi ◽

Ahmad Qasem ◽

Saleh A. Naser

Keyword(s):

Cigarette Smoke ◽

Bowel Disease ◽

Mycobacterium Avium Subspecies Paratuberculosis ◽

Microbial Infection ◽

Inflammatory Bowel ◽

Anti Inflammatory ◽

Inflammatory Phenotypes

Cigarette smoke (CS) has adverse effects in patients with Crohn’s disease (CD), an inflammatory bowel disease (IBD) that has been associated with microbial infection, immuno-dysregulation, and mucosal dysfunction. However, CS seems to provide relief and protection to patients with another IBD known as ulcerative colitis (UC). These two subsets are featured as M1- and M2-mediated responses, respectively. Nicotine is the most active, addictive, and studied ingredient in CS. The mechanism of how nicotine and/or other CS ingredients induce pro-inflammatory or anti-inflammatory phenotypes in IBD patients remains under investigation. Our most recent in vitro nicotine study provided significant insights toward understanding the contradictory effects of nicotine on IBD patients, and it elucidated the mechanistic role of α7nAChR in modulation of macrophages in tobacco smokers. Shifting the beneficial effect of nicotine to a harmful outcome in CD patients was linked to a nicotine-microbe interaction that supports a microbial etiology in CD pathogenesis. Among the most debated pathogens in CD etiology is Mycobacterium avium subspecies paratuberculosis (MAP). Other studies associated nicotine with upregulation of miR-124 expression in macrophages, which led to anti-inflammatory response. This review discusses published work on the role of nicotine in modulation of the innate immune response and subsequent signaling in macrophages in IBD subsets.

Medical Cannabis and Cannabinoids: An Option for the Treatment of Inflammatory Bowel Disease and Cancer of the Colon?

Medical Cannabis and Cannabinoids ◽

10.1159/000489036 ◽

2018 ◽

Vol 1 (1) ◽

pp. 28-35 ◽

Cited By ~ 1

Author(s):

Magdalena Grill ◽

Carina Hasenoehrl ◽

Martin Storr ◽

Rudolf Schicho

Keyword(s):

Bowel Disease ◽

Intestinal Inflammation ◽

Medical Cannabis ◽

Pilot Studies ◽

Inflammatory Bowel ◽

Multiple Sclerosis Patients ◽

In Vitro Data

In the past few years, we have witnessed a surge of new reports dealing with the role of cannabinoids, synthetic as well as herbal, in the mechanisms of inflammation and carcinogenesis. However, despite the wealth of in vitro data and anecdotal reports, evidence that cannabinoids could act as beneficial drugs in inflammatory bowel disease (IBD) or in neoplastic development of the human gastrointestinal tract is lacking. Some insight into the effects of medical Cannabis (usually meaning dried flowers) and cannabinoids in IBD has been gained through questionnaires and small pilot studies. As to colorectal cancer, only preclinical data are available. Currently, Δ9-tetrahydrocannabinol (THC) and its synthetic forms, dronabinol and nabilone, are used as an add-on treatment to alleviate chronic pain and spasticity in multiple sclerosis patients as well as chemotherapy-induced nausea. The use of medical Cannabis is authorized only in a limited number of countries. None of the mentioned substances are currently indicated for IBD. This review is an update of our knowledge on the role of cannabinoids in intestinal inflammation and carcinogenesis and a discussion on their potential therapeutic use.

Role of stress and intestinal barrier dysfunction in inflammatory bowel disease

World Chinese Journal of Digestology ◽

10.11569/wcjd.v24.i21.3248 ◽

2016 ◽

Vol 24 (21) ◽

pp. 3248

Author(s):

Shu-Ling Wang ◽

Sheng-Bing Zhao ◽

Jun Fang ◽

Dan Ma ◽

Hong-Yu Fu ◽

...

Keyword(s):

Bowel Disease ◽

Intestinal Barrier ◽

Barrier Dysfunction ◽

Intestinal Barrier Dysfunction ◽

Falk Symposium - Inflammatory Bowel Disease — Diagnostic and Therapeutic Strategies ◽

Role of the intestinal barrier in inflammatory bowel disease

10.1007/978-1-4020-6116-5_11 ◽

2007 ◽

pp. 109-114

Author(s):

S. Zeissig ◽

F. Heller ◽

J. -D. Schulzke

Keyword(s):

Bowel Disease ◽

Intestinal Barrier ◽

Role of the intestinal barrier in inflammatory bowel disease

World Journal of Gastroenterology ◽

10.3748/wjg.14.401 ◽

2008 ◽

Vol 14 (3) ◽

pp. 401 ◽

Cited By ~ 168

Author(s):

Mike G Laukoetter ◽

Porfirio Nava ◽

Asma Nusrat

Keyword(s):

Bowel Disease ◽

Intestinal Barrier ◽

Intestinal Anti-Inflammatory Effect of a Peptide Derived from Gastrointestinal Digestion of Buffalo (Bubalus bubalis) Mozzarella Cheese

Nutrients ◽

10.3390/nu11030610 ◽

2019 ◽

Vol 11 (3) ◽

pp. 610 ◽

Cited By ~ 8

Author(s):

Gian Tenore ◽

Ester Pagano ◽

Stefania Lama ◽

Daniela Vanacore ◽

Salvatore Di Maro ◽

...

Keyword(s):

Bowel Disease ◽

Therapeutic Potential ◽

Intestinal Barrier ◽

Bubalus Bubalis ◽

Epithelial Junctions ◽

Inflammatory Bowel ◽

Anti Inflammatory

Under physiological conditions, the small intestine represents a barrier against harmful antigens and pathogens. Maintaining of the intestinal barrier depends largely on cell–cell interactions (adherent-junctions) and cell–matrix interactions (tight-junctions). Inflammatory bowel disease is characterized by chronic inflammation, which induces a destructuring of the architecture junctional epithelial proteins with consequent rupture of the intestinal barrier. Recently, a peptide identified by Bubalus bubalis milk-derived products (MBCP) has been able to reduce oxidative stress in intestinal epithelial cells and erythrocytes. Our aim was to evaluate the therapeutic potential of MBCP in inflammatory bowel disease (IBD). We studied the effect of MBCP on (i) inflamed human intestinal Caco2 cells and (ii) dinitrobenzene sulfonic acid (DNBS) mice model of colitis. We have shown that MBCP, at non-cytotoxic concentrations, both in vitro and in vivo induced the adherent epithelial junctions organization, modulated the nuclear factor (NF)-κB pathway and reduced the intestinal permeability. Furthermore, the MBCP reverted the atropine and tubocurarine injury effects on adherent-junctions. The data obtained showed that MBCP possesses anti-inflammatory effects both in vitro and in vivo. These results could have an important impact on the therapeutic potential of MBCP in helping to restore the intestinal epithelium integrity damaged by inflammation.