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TNF-? and INF-? primed canine stem cell-derived extracellular vesicles alleviate experimental murine colitis.

ABSTRACT: The inflammatory bowel diseases (IBD) are characterized by relapsing inflammation and immune activation diseases of the gastrointestinal tract. Extracellular vesicles, which elicit similar biological activity to the stem cell themselves, have been used experimentally to treat dextran sulfate sodium (DSS)-induced colitis in murine models though immunosuppressive potential. In this study, we investigated whether the Extracellular vesicles (EVs) obtained by stimulating inflammatory cytokine on canine adipose mesenchymal stem cells (cASC) improved anti-inflammatory and/or immunosuppressive potential of EVs, and/or their ability to alleviate inflammation in colitis. We also explored the correlation between immune cells and the inflammatory repressive effect of primed EVs. Pro-inflammatory cytokines such as TNF-? and IFN-? increased immunosuppressive protein such as HGF, TSG-6, PGE2 and TGF-? in EVs. Moreover, the anti-inflammatory effect of EVs was improved through pretreatment with inflammatory cytokines. Importantly, EVs obtained from primed stem cells effectively induced macrophage polarization toward an anti-inflammatory M2 phenotype and suppressed activated immunity by enhancing regulatory T cells in inflamed colon in mice. Our results provide a new and effective therapy for the EVs obtained from ASC stimulated with TNF-? and IFN-? against not only IBD, but also immune-mediated disease.

SUBMITTER: An JH

PROVIDER: S-EPMC7005871 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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TNF-α and INF-γ primed canine stem cell-derived extracellular vesicles alleviate experimental murine colitis.

An Ju-Hyun JH Li Qiang Q Bhang Dong-Ha DH Song Woo-Jin WJ Youn Hwa-Young HY

Scientific reports 20200207 1

The inflammatory bowel diseases (IBD) are characterized by relapsing inflammation and immune activation diseases of the gastrointestinal tract. Extracellular vesicles, which elicit similar biological activity to the stem cell themselves, have been used experimentally to treat dextran sulfate sodium (DSS)-induced colitis in murine models though immunosuppressive potential. In this study, we investigated whether the Extracellular vesicles (EVs) obtained by stimulating inflammatory cytokine on cani ...[more]

PMID: 32034203

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Project description:Microbiological treatments are expected to have a role in the future management of inflammatory bowel disease (IBD). Clostridium butyricum (C. butyricum) is a probiotic microorganism that exhibits beneficial effects on various disease conditions. Although many studies have revealed that C. butyricum provides protective effects in mice with colitis, the way C. butyricum establishes beneficial results in the host remains unclear. In this study, we investigated the mechanisms by which C. butyricum modifies the gut microbiota, produces bacterial metabolites that may be involved, and, specifically, how microbial extracellular vesicles (EVs) positively influence IBD, using a dextran sulfate sodium (DSS)-induced colitis murine model in mice. First, we showed that C. butyricum provides a protective effect against colitis, as evidenced by the prevention of body weight loss, a reduction in the disease activity index (DAI) score, a shortened colon length, decreased histology score, and an improved gut barrier function, accompanied by reduced levels of pathogenic bacteria, including Escherichia/Shigella, and an increased relative abundance of butyrate-producing Clostridium sensu stricto-1 and Butyricicoccus. Second, we also confirmed that the gut microbiota and metabolites produced by C. butyricum played key roles in the attenuation of DSS-induced experimental colitis, as supported by the profound alleviation of colitis effects following fecal transplantation or fecal filtrate insertion supplied from C. butyricum-treated mice. Finally, C. butyricum-derived EVs protected the gut barrier function, improved gut microbiota homeostasis in ulcerative colitis, and contributed to overall colitis alleviation. IMPORTANCE This study indicated that C. butyricum provided a prevention effect against colitis mice, which involved protection of the intestinal barrier and positively regulating gut microbiota. Furthermore, we confirmed that the gut microbiota and metabolites that were induced by C. butyricum also contributed to the attenuation of DSS-induced colitis. Importantly, C. butyricum-derived EVs showed an effective impact in alleviating colitis.

Dataset Information

TNF-? and INF-? primed canine stem cell-derived extracellular vesicles alleviate experimental murine colitis.

Publications

TNF-α and INF-γ primed canine stem cell-derived extracellular vesicles alleviate experimental murine colitis.

Similar Datasets

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