Search results for "Intestinal epithelium"

Melatonin reduces inflammatory response in human intestinal epithelial cells stimulated by interleukin‐1β

2019

Melatonin is the main secretory product of the pineal gland, and it is involved in the regulation of periodic events. A melatonin production independent of the photoperiod is typical of the gut. However, the local physiological role of melatonin at the intestinal tract is poorly characterized. In this study, we evaluated the anti-inflammatory activities of melatonin in an in vitro model of inflamed intestinal epithelium. To this purpose, we assessed different parameters usually associated with intestinal inflammation using IL-1 beta-stimulated Caco-2 cells. Differentiated monolayers of Caco-2 cells were preincubated with melatonin (1 nmol/L-50 mu mol/L) and then exposed to IL-1 beta. After …

The unusual structure of Ruminococcin C1 antimicrobial peptide confers clinical properties.

2020

The emergence of superbugs developing resistance to antibiotics and the resurgence of microbial infections have led scientists to start an antimicrobial arms race. In this context, we have previously identified an active RiPP, the Ruminococcin C1, naturally produced by Ruminococcus gnavus E1, a symbiont of the healthy human intestinal microbiota. This RiPP, subclassified as a sactipeptide, requires the host digestive system to become active against pathogenic Clostridia and multidrug-resistant strains. Here, we report its unique compact structure on the basis of four intramolecular thioether bridges introduced post-translationally by a specific radical-SAM sactisynthase. This structure con…

2018

Patients with inflammatory bowel disease (IBD) are susceptible to thromboembolism. Interestingly, IBD occurs less frequently in patients with inherited bleeding disorders. Therefore, we analyzed whether F9-deficiency is protective against the onset of acute colitis in a genetic hemophilia B mouse model. In the 3.5% dextran sulfate sodium (DSS)-induced colitis model, F9-deficient mice were protected from body-weight loss and had a reduced disease activity score. We detected decreased colonic myeloperoxidase activity and decreased CXCL1 levels in DSS-treated F9-deficient mice compared with wild-type (WT) littermate controls, indicating decreased neutrophil infiltration. Remarkably, we identif…

WNT2 activation through proximal germline deletion predisposes to small intestinal neuroendocrine tumors and intestinal adenocarcinomas

2021

Abstract Many hereditary cancer syndromes are associated with an increased risk of small and large intestinal adenocarcinomas. However, conditions bearing a high risk to both adenocarcinomas and neuroendocrine tumors are yet to be described. We studied a family with 16 individuals in four generations affected by a wide spectrum of intestinal tumors, including hyperplastic polyps, adenomas, small intestinal neuroendocrine tumors, and colorectal and small intestinal adenocarcinomas. To assess the genetic susceptibility and understand the novel phenotype, we utilized multiple molecular methods, including whole genome sequencing, RNA sequencing, single cell sequencing, RNA in situ hybridization…

Metabolic adaptation in the human gut microbiota during pregnancy and the first year of life

2018

Abstract Background The relationship between the gut microbiome and the human host is dynamic and we may expect adjustments in microbiome function if host physiology changes. Metatranscriptomic approaches should be key in unraveling how such adjustments occur. Methods We employ metatranscriptomic sequencing analyses to study gene expression in the gut microbiota of infants through their first year of life, and of their mothers days before delivery and one year afterwards. Findings In infants, hallmarks of aerobic metabolism disappear from the microbial metatranscriptome as development proceeds, while the expression of functions related to carbohydrate transport and metabolism increases and …

Identification of epithelial gaps in human small and large intestine by confocal endomicroscopy.

2007

Background & Aims: Confocal endomicroscopy is an emerging technology that poses the endoscopist with challenges for identifying epithelial structures in the human intestine. We have shown previously that the murine intestinal epithelium is punctuated by gaps caused by cell shedding. The goals of this study were to determine if confocal endomicroscopy could resolve the presence of human epithelial gaps and whether a proinflammatory cytokine could increase cell shedding. Methods: Intestinal mucosa was imaged after staining with acriflavine. Confocal endomicroscopy of 17 patients yielded 6277 images from the human terminal ileum and rectum. Results were validated by parallel studies of anesthe…

GLP-2: What do we know? What are we going to discover?

2014

Glucagon-like peptide 2 [GLP-2] is a 33-amino acid peptide released from the mucosal enteroendocrine L-cells of the intestine. The actions of GLP-2 are transduced by the GLP-2 receptor [GLP-2R], which is localized in the neurons of the enteric nervous system but not in the intestinal epithelium, indicating an indirect mechanism of action. GLP-2 is well known for its trophic role within the intestine and interest in GLP-2 is now reviving based on the approval of the GLP-2R agonist for treatment of short bowel syndrome [SBS]. Recently it also seems to be involved in glucose homeostasis. The aim of this review is to outline the importance of neuroendocrine peptides, specifically of GLP-2 in th…

Intestinal Scavenger Receptors Are Involved in Vitamin K 1 Absorption

2014

International audience; Vitamin K-1 (phylloquinone) intestinal absorption is thought to be mediated by a carrier protein that still remains to be identified. Apical transport of vitamin K-1 was examined using Caco-2 TC-7 cell monolayers as a model of human intestinal epithelium and in transfected HEK cells. Phylloquinone uptake was then measured ex vivo using mouse intestinal explants. Finally, vitamin K-1 absorption was compared between wild-type mice and mice overexpressing scavenger receptor class B type I (SR-BI) in the intestine and mice deficient in cluster determinant 36 (CD36). Phylloquinone uptake by Caco-2 cells was saturable and was significantly impaired by co-incubation with al…

Mast Cells Infiltrating Inflamed or Transformed Gut Alternatively Sustain Mucosal Healing or Tumor Growth.

2015

Abstract Mast cells (MC) are immune cells located next to the intestinal epithelium with regulatory function in maintaining the homeostasis of the mucosal barrier. We have investigated MC activities in colon inflammation and cancer in mice either wild-type (WT) or MC-deficient (KitW-sh) reconstituted or not with bone marrow-derived MCs. Colitis was chemically induced with dextran sodium sulfate (DSS). Tumors were induced by administering azoxymethane (AOM) intraperitoneally before DSS. Following DSS withdrawal, KitW-sh mice showed reduced weight gain and impaired tissue repair compared with their WT littermates or KitW-sh mice reconstituted with bone marrow-derived MCs. MCs were localized i…

An approach to As(III) and As(V) bioavailability studies with Caco-2 cells

2005

Foods and drinking water are the main sources of human exposure to inorganic arsenic [As(III) and As(V)]. After oral ingestion, the intestinal epithelium is the first barrier to absorption of these species. A human intestinal cell line (Caco-2) was used to evaluate cell retention and transport of As(III) (15.6-156.0 microM) and/or As(V) (15.4-170.6 microM). Cell monolayer integrity, cell viability, membrane damage and effects on cell metabolism were evaluated. Only the highest concentrations assayed [As(III): 156.0 microM; As(V): 170.6 microM] produced a cytotoxic effect with different cellular targets: As(III) altered the permeability of tight junctions, and As(V) caused uncoupling of the …