Dataset Information

Apple polyphenols require T cells to ameliorate dextran sulfate sodium-induced colitis and dampen proinflammatory cytokine expression.

ABSTRACT: Human IBD, including UC and Crohn's disease, is characterized by a chronic, relapsing, and remitting condition that exhibits various features of immunological inflammation and affects at least one/1000 people in Western countries. Polyphenol extracts from a variety of plants have been shown to have immunomodulatory and anti-inflammatory effects. In this study, treatment with APP was investigated to ameliorate chemically induced colitis. Oral but not peritoneal administration of APP during colitis induction significantly protected C57BL/6 mice against disease, as evidenced by the lack of weight loss, colonic inflammation, and shortening of the colon. APP administration dampened the mRNA expression of IL-1β, TNF-α, IL-6, IL-17, IL-22, CXCL9, CXCL10, CXCL11, and IFN-γ in the colons of mice with colitis. APP-mediated protection requires T cells, as protection was abated in Rag-1(-/-) or TCRα(-/-) mice but not in IL-10(-/-), IRF-1(-/-), μMT, or TCRδ(-/-) mice. Administration of APP during colitis to TCRα(-/-) mice actually enhanced proinflammatory cytokine expression, further demonstrating a requirement for TCRαβ cells in APP-mediated protection. APP treatment also inhibited CXCR3 expression by TCRαβ cells, but not B or NK cells, in the colons of mice with colitis; however, depletion of CD4(+) or CD8(+) T cells alone did not abolish APP-mediated protection. Collectively, these results show that oral administration of APP protects against experimental colitis and diminishes proinflammatory cytokine expression via T cells.

SUBMITTER: Skyberg JA

PROVIDER: S-EPMC3236552 | biostudies-literature | 2011 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Apple polyphenols require T cells to ameliorate dextran sulfate sodium-induced colitis and dampen proinflammatory cytokine expression.

Skyberg Jerod A JA Robison Amy A Golden Sarah S Rollins Maryclare F MF Callis Gayle G Huarte Eduardo E Kochetkova Irina I Jutila Mark A MA Pascual David W DW

Journal of leukocyte biology 20110621 6

Human IBD, including UC and Crohn's disease, is characterized by a chronic, relapsing, and remitting condition that exhibits various features of immunological inflammation and affects at least one/1000 people in Western countries. Polyphenol extracts from a variety of plants have been shown to have immunomodulatory and anti-inflammatory effects. In this study, treatment with APP was investigated to ameliorate chemically induced colitis. Oral but not peritoneal administration of APP during coliti ...[more]

PMID: 21693591

Similar Datasets

Project description:This study aimed to investigate the ameliorative effect of the polysaccharides of Panax quinquefolius (WQP) on ulcerative colitis (UC) induced by dextran sulfate sodium (DSS) in mice and to explore its mechanism. Male C57BL/6J mice were randomly divided into the control group (C), model group (DSS), positive control mesalazine (100 mg/kg, Y) group, and low (50 mg/kg, L), medium (100 mg/kg, M) and high dose (200 mg/kg, H) of WQP groups. The UC model was induced by free drinking water with 2.5% DSS for 7 days. During the experiment, the general condition of the mice was observed, and the disease activity index (DAI) was scored. The conventional HE staining was used to observe pathological changes in mice's colon, and the ELISA method was used to detect the levels of interleukin-6 (IL-6), IL-4, IL-8, IL-10, IL-1β and tumor necrosis factor-α (TNF-α) in mice's colon. The changes in gut microbiota in mice were detected by high-throughput sequencing; the concentration of short-chain fatty acids (SCFAs) was determined by gas chromatography; the expression of related proteins was detected by Western blot. Compared with the DSS group, the WQP group showed a significantly lower DAI score of mice and an alleviated colon tissue injury. In the middle- and high-dose polysaccharides groups, the levels of pro-inflammatory cytokines IL-6, IL-8, IL-1β and TNF-α in the colonic tissue were significantly decreased (P<0.05), while the levels of IL-4 and IL-10 were significantly increased (P<0.05). The 16S rRNA gene sequencing results showed that different doses of WQP could regulate the composition and diversity of gut microbiota and improve its structure. Specifically, at the phylum level, group H showed an increased relative abundance of Bacteroidetes and a decreased relative abundance of Firmicutes compared with the DSS group, which was closer to the case in group C. At the family level, the relative abundance of Rikenellaceae in L, M and H groups increased significantly, close to that in group C. At the genus level, the relative abundance of Bacteroides, Shigella and Oscillospira in the H group increased significantly, while that of Lactobacillus and Prevotella decreased significantly. The high-dose WQP group could significantly increase the contents of acetic acid, propionic acid, butyric acid, and total SCFAs. Different doses of WQP also increased the expression levels of tight junction proteins ZO-1, Occludin and Claudin-1. To sum up, WQP can regulate the gut microbiota structure of UC mice, accelerate the recovery of gut microbiota, and increase the content of Faecal SCFAs and the expression level of tight junction proteins in UC mice. This study can provide new ideas for the treatment and prevention of UC and theoretical references for the application of WQP.

Project description:Cucurbitacins have a variety of bioactivities, such as anticancer, anti-inflammatory, antidepressant-like, and antiviral effects, but their pharmacological effect in ulcerative colitis (UC) has not been reported until now. Thus, this study aims to investigate the preventive effects of Xuedan sustained release pellets (XSPs) on UC rats and the underlying mechanisms. XSPs were prepared by extracting cucurbitacins from Hemsleya. Experimental UC rats were induced by the intake of 4% dextran sulfate sodium (DSS) for a week and treated with different doses of XSP (0.95, 1.90, and 3.8 mg/kg). The body weight, colon length, disease activity index (DAI), and histological changes of colonic tissue were measured. In addition, the expressions of pro-inflammatory cytokines were detected by using the enzyme-linked immunosorbent assay. Pathways involved in the intestinal inflammation were targeted by RNA-sequencing. Moreover, the changes of gut microbial diversity and composition were analyzed by the 16SrNA analysis and the contents of short-chain fatty acids (SCFAs) were detected by GC-MS. The results revealed that XSP intervention greatly restored the weight loss and colonic shortening (p < 0.05) and reduced the raised DAI scores, myeloperoxidase, and nitric oxide activities in UC in rats (p < 0.05). XSP administration also downregulated the protein levels of pro-inflammatory factors IL-1β, IL-6, and TNF-α. Notably, it was found that XSP considerably suppressed the activation of the MAPK signaling pathway. In addition, XSP treatment improved the balance of gut microbiota that was disturbed by DSS. The beneficial bacteria Lachnospiraceae_NK4A136 group and Lactobacillus at the genus level significantly increased in the XSP group, which had decreased with the use of DSS (p < 0.05). Pathogenic bacteria including Escherichia-Shigella and Bacteroides in UC in rats were reduced by XSP intervention. Furthermore, XSP significantly elevated the production of SCFAs in UC in rats (p < 0.05). These alterations in inflammatory status were accompanied with changes in gut microbiota diversity and SCFA production. In conclusion, XSP exhibited protective effects against DSS-induced UC in rats. XSP treatment decreased inflammation via modulation of gut microbiota composition and SCFA production.

Dataset Information

Apple polyphenols require T cells to ameliorate dextran sulfate sodium-induced colitis and dampen proinflammatory cytokine expression.

Publications

Apple polyphenols require T cells to ameliorate dextran sulfate sodium-induced colitis and dampen proinflammatory cytokine expression.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets