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treatment of murine colitis by saccharomyces boulardii secreting atrial natriuretic peptide
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نویسنده
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liu cheng-hao ,chang jen-hsuan ,chang you-chiun ,mou kurt yun
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منبع
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journal of molecular medicine - 2020 - دوره : 98 - شماره : 12 - صفحه:1675 -1687
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چکیده
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Inflammatory bowel disease is a lifelong disorder that involves chronic inflammation in the small and large intestines. current therapies, including aminosalicylates, corticosteroids, and anti-inflammatory biologics, can only alleviate the symptoms and often cause adverse effects with long-term usage. engineered probiotics provide an alternative approach to treat inflammatory bowel disease in a self-renewable and local delivery fashion. in this work, we utilized a yeast probiotic saccharomyces boulardii for this purpose. we developed a robust method to integrate recombinant genes into the ty elements of s. boulardii. stable yeast cell lines that secreted various anti-inflammatory proteins, including il-10, tnfr1-ecd, alkaline phosphatase, and atrial natriuretic peptide (anp), were successfully created and investigated for their efficacies to the dss-induced colitis in mice through oral administration. while il-10, tnfr1-ecd, and alkaline phosphatase did not show therapeutic effects, the anp-secreting s. boulardii effectively ameliorated the mouse conditions as reflected by the improvements in body weight, disease activity index, and survival rate. a post-mortem examination revealed that the anp-treated mice exhibited significant downregulations of tnf-α and il-1β and an upregulation of il-6 in colon tissues. this observation is consistent with the previous reports showing that tnf-α and il-1β are responsible for initiating the pathogenesis, whereas il-6 plays a protective role in colitis. overall, we demonstrated that s. boulardii is a safe and robust vehicle for recombinant protein delivery in the gastrointestinal tract, and anp is a potential anti-inflammatory drug for colitis treatment.
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کلیدواژه
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inflammatory bowel diseases ,dss-induced colitis ,saccharomyces boulardii ,probiotics ,atrial natriuretic peptide
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آدرس
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academia sinica, institute of biomedical sciences, taiwan. national yang-ming university and academia sinica, taiwan international graduate program in molecular medicine, taiwan, academia sinica, institute of biomedical sciences, taiwan, academia sinica, institute of biomedical sciences, taiwan, academia sinica, institute of biomedical sciences, taiwan
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Authors
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