Tu1256 - Optimization of a Chronic Colitis Model in Mice Induced by Dextran Sulphate Sodium (DSS) and Effects of Drugs Thereon

Abstract Intestinal fibrosis and stenosis are common complications of Crohn’s disease [CD], frequently requiring surgery. Anti-inflammatory strategies can only partially prevent fibrosis; hence, anti-fibrotic therapies remain an unmet clinical need. Oxysterols are oxidised cholesterol derivatives with important roles in various biological processes. The enzyme cholesterol 25-hydroxylase [CH25H] converts cholesterol to 25-hydroxycholesterol [25-HC], which modulates immune responses and oxidative stress. In human intestinal samples from CD patients, we found a strong correlation of CH25H mRNA expression with the expression of fibrosis markers. We demonstrate reduced intestinal fibrosis in mice deficient for the CH25H enzyme, using the sodium dextran sulphate [DSS]-induced chronic colitis model. Additionally, using a heterotopic transplantation model of intestinal fibrosis, we demonstrate reduced collagen deposition and lower concentrations of hydroxyproline in CH25H knockouts. In the heterotopic transplant model, CH25H was expressed in fibroblasts. Taken together, our findings indicate an involvement of oxysterol synthesis in the pathogenesis of intestinal fibrosis.

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Regulatory B cells contribute to the alleviation of colitis induced by Dextran Sulphate Sodium after H.pylori infection

10.1101/305094 ◽

2018 ◽

Author(s):

Xia Li ◽

Jiang Tan ◽

Feng Zhang ◽

Qian Xue ◽

Ning Wang ◽

...

Keyword(s):

B Cells ◽

Mrna Expression ◽

Inflammatory Cytokines ◽

Critical Role ◽

Treated Group ◽

Dextran Sulphate ◽

Regulatory B Cells ◽

Chronic Colitis ◽

Dextran Sulphate Sodium ◽

Pro Inflammatory Cytokines

BackgroundEpidemiological studies showed that there was an inverse relationship between Helicobacter pylori infection and the incidence of inflammatory bowel disease. Our previous research indicated that the regulatory immune responses induced by H.pylori infection were not limited to gastric mucosa, and the balance of intestinal mucosal immunity was influenced. In this study, we investigated the role of the regulatory B cells in the effects of the H.pylori infection on acute and chronic colitis induced by dextran sulphate sodium.MethodsMice were infected with H.pylori and then colitis was induced by 3% DSS, the CD19+IL-10+Breg cells and CD4+CD25+Foxp3+Treg cells in blood、 spleen、 mesenteric lymph nodes (MLN)、 Peyer’s Patches (PP) and gastrointestinal mucosa were measured and examined. The anti– and pro-inflammatory cytokines were also detected at mRNA level.ResultsIn the acute and chronic colitis groups, DAI and colonic histological scores reduced significantly and colon length shorted less; the anti-inflammatory cytokines mRNA expression upregulated while the pro-inflammatory cytokines mRNA expression downregulated in colonic mucosa; and the percentages of CD19+IL-10+Breg cells in blood spleen MLN、 PP were higher in the H.pylori/DSS co-treated group compared with the DSS treated group.ConclusionH.pylori infection can alleviate the acute and chronic colitis induced by DSS. CD19+IL-10+Breg cells may play a critical role in the alleviation of acute and chronic colitis following H.pylori infection.

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