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Decitabine attenuates dextran sodium sulfate?induced ulcerative colitis through regulation of immune regulatory cells and intestinal barrier.

ABSTRACT: To investigate the effect of decitabine on the regulation of intestinal barrier function in mice with inflammatory bowel disease, an experimental model of colitis was established via drinking water with dextran sulfate sodium (DSS). Hematoxylin and eosin staining was used to observe the pathological changes of the colon. Cytokine production was measured by an ELISA assay. Flow cytometry was used to measure the level of regulatory T cells. Immunofluorescence, immunohistochemistry and western blot analyses detected the protein expression and distribution in colon tissue. Following the administration of decitabine, the symptoms of intestinal inflammation in the mice were significantly relieved; the expression of IL?17 was decreased, and the levels of TGF?? and IL?10 were increased. In addition, the induction of forkhead box P3 (Foxp3) in naive T cells increased the proportion of CD4+ Foxp3+ T cells in CD4+ T cells. Furthermore, decitabine increased the levels of zonular occludens?1 and occludin, and inhibited the phosphorylation of ERK1/2, JNK and p38. In conclusion, the present study suggested that decitabine could alleviate DSS?induced impaired colon barrier and the weight loss, mucus and bloody stools in mice by releasing the inhibitory factor IL?10, reducing the pro?inflammatory factor IL?17, activating CD4+ Foxp3+ T cells and inhibiting the activation of the MAPK pathway.

SUBMITTER: Su C

PROVIDER: S-EPMC7307821 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Decitabine attenuates dextran sodium sulfate‑induced ulcerative colitis through regulation of immune regulatory cells and intestinal barrier.

Su Chang C Liu Shaoqun S Ma Xiaoying X Yang Xiaotong X Liu Jianwen J Zheng Peiyong P Cao Yiou Y

International journal of molecular medicine 20200518 2

To investigate the effect of decitabine on the regulation of intestinal barrier function in mice with inflammatory bowel disease, an experimental model of colitis was established via drinking water with dextran sulfate sodium (DSS). Hematoxylin and eosin staining was used to observe the pathological changes of the colon. Cytokine production was measured by an ELISA assay. Flow cytometry was used to measure the level of regulatory T cells. Immunofluorescence, immunohistochemistry and western blot ...[more]

PMID: 32468024

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Project description:Periplaneta americana, a magic medicinal insect being present for over 300 million years, exhibits desirable therapeutic outcome for gastrointestinal ulcer treatment. Nowadays, P. americana ethanol extract (PAE) has been shown to ameliorate ulcerative colitis (UC) by either single-use or in combination with other therapeutic agents in clinics. However, its underlying mechanisms are still seldom known. Herein, we investigated the anti-UC activity of PAE by alleviating intestinal inflammation and regulating the disturbed gut microbiota structure in dextran sulfate sodium (DSS)-induced UC rats. Based on multiple constitute analyses by HPLC for quality control, PAE was administrated to DSS-induced UC rats by oral gavage for 2 weeks. The anti-UC effect of PAE was evaluated by inflammatory cytokine production, immunohistochemical staining, and gut microbiota analysis via 16S rRNA sequencing. As a result, PAE remarkably attenuated DSS-induced UC in rats. The colonic inflammatory responses manifested as decreased colonic atrophy, intestinal histopathology scores and inflammatory cytokines. In addition, PAE improved the intestinal barrier function via activating Keap1/Nrf-2 pathway and promoting the expressions of tight junction proteins. It was observed that the UC rats showed symptoms of gut microbial disturbance, i.e., the increased Firmicutes/Bacteroidetes ratio and the significantly decreased probiotics such as Lactobacillus, Roseburia, and Pectobacterium, which were negatively correlated with these detected pro-inflammatory cytokines (secreted by immune CD4+ T cells, and including IFN-γ, TNF-α, IL-6, IL-8, IL-17, IL-1β). Besides, PAE administration regulated the abnormal intestinal microbial composition and made it similar to that in normal rats. Therefore, PAE could attenuate the DSS-induced UC in rats, by means of ameliorating intestinal inflammation, improving intestinal barrier function, and regulating the disturbed gut microbiota, especially improving beneficial intestinal flora growth, modulating the flora structure, and restoring the intestinal-immune system.

Dataset Information

Decitabine attenuates dextran sodium sulfate?induced ulcerative colitis through regulation of immune regulatory cells and intestinal barrier.

Publications

Decitabine attenuates dextran sodium sulfate‑induced ulcerative colitis through regulation of immune regulatory cells and intestinal barrier.

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