Dataset Information

Inflammation promotes stomach epithelial defence by stimulating the secretion of antimicrobial peptides in the mucus

ABSTRACT: Mucus is a protein-based gel secreted by specialized epithelial cells that protects the gastrointestinal mucosa from microorganism attack and irritating agents. Experiments in mice have demonstrated that when the mucosa is infected or inflamed, the mucus becomes enriched with broad-spectrum bactericidal compounds known as antimicrobial peptides (AMPs). Although AMP gene expression has been identified in both immune and epithelial cells, how inflammation regulates AMP secretion in the mucus remains unclear, and the efficacy of AMP-enriched mucus in defending against microorganisms has not been assessed. We have developed a “mucosoid” culture model that simulates the healthy human stomach epithelium. In these cultures, epithelial cells form a barrier and can differentiate into mucus-secreting cells. The accumulation of mucus on the apical side facilitates the detection of AMPs and the assessment of their bactericidal properties. We report that cytokines TNFa, IL1b and IFNg enhance the secretion of the AMPs lactotransferrin, lipocalin2, C3A, and CXCL9 into the mucus. The mucus from inflamed cells which contains the aforementioned AMPs partially kills Helicobacter pylori, the sole stomach pathogen. However, H. pylori can inhibit this defence by reducing AMP gene expression in inflamed epithelial cells. These results reveal that secreted mucus is a relevant effector of epithelial immunity but pathogens like H. pylori can subvert these defences to persist in the mucosa.

ORGANISM(S): Homo sapiens

PROVIDER: GSE268591 | GEO | 2024/09/09

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Inflammatory bowel diseases (IBD) in humans are characterized by chronic inflammation and gastrointestinal tissue damage, caused by a combination of genetic and environmental factors. It has been largely documented that IBD frequently lead to colorectal cancers (CRC). The identification of causative factors of IBD is thus essential to understand CRC progression and develop therapeutical approaches. Models have been described in which molecular alterations are combined with inflammatory treatments in order to recapitulate IBD-associated CRC. Here, we describe a mouse line, Î±6fl/fl Villin-Cre, in which inactivation of the gene encoding the integrin alpha-6 subunit (ITGA6) specifically in the intestinal mucosa results into chronic inflammation and intestinal carcinogenesis. In these mice, the loss of integrin alpha-6 beta-4, a receptor mediating the attachment of epithelial cells to laminins, leads to epithelial detachment, hyperplasia, chronic inflammation, rectal prolapses, and ultimately adenocarcinomas. Alterations of differentiation affecting mucus secreting (goblet) cells as well as changes in expression of essential intestinal transcription factors were detected. Thus alpha-6 beta-4 integrin is a key factor for the maintenance of intestinal integrity and its loss may represent a risk factor for tumor progression associated with IBD. Transcriptome analysis of RNA from normal versus inflamed and carcinomatous rectal mucosa of Î±6 integrin deficient intestinal epithelium mice was performed. RNAs were prepared from 5 adenocarcinomas, which were macrodissected from the rectal prolapses and 4 flanking inflamed rectal mucosa of 53-80 week-old Î±6fl/fl Villin-Cre mice. RNAs from normal rectal mucosa were obtained by rectum scraping from 4 matched control animals. The transcriptome analysis was performed using the Affymetrix Mouse Gene 1.0 ST arrays. Images were processed using affymetrix GeneChipÂ® Command ConsoleÂ® Software (AGCC) (version 2.0) and numerical value were generated using Affymetrix Expression Consoleâ¢ Software (version 1.1).

Dataset Information

Inflammation promotes stomach epithelial defence by stimulating the secretion of antimicrobial peptides in the mucus

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets