Amelioration of Murine Colitis by Attenuated Salmonella choleraesuis Encoding Interleukin-19

编码白细胞介素-19 的减毒猪霍乱沙门氏菌对小鼠结肠炎的改善作用

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作者:Shih-Yao Chen, Chun-Ting Chu, Mei-Lin Yang, Jian-Da Lin, Chung-Teng Wang, Che-Hsin Lee, I-Chen Lin, Ai-Li Shiau, Pin Ling, Chao-Liang Wu

Abstract

The imbalance of mucosal immunity in the lower gastrointestinal tract can lead to chronic inflammatory bowel diseases (IBDs), including Crohn's disease and ulcerative colitis. IBD is a chronic inflammatory disorder that causes small and/or large intestines ulceration. According to previous studies, recombinant interleukin (IL)-10 protein and genetically modified bacteria secreting IL-10 ameliorate dextran sulfate sodium (DSS)-induced colitis in mice. IL-19 is a transcriptional activator of IL-10 and can alter the balance of T helper 1 (Th)1/Th2 cells in favor of Th2. In this study, we aimed to investigate whether the expression of the murine IL-19 gene carried by Salmonella choleraesuis (S. choleraesuis) could ameliorate murine IBD. Our results showed that the attenuated S. choleraesuis could carry and express the IL-19 gene-containing plasmid for IBD gene therapy by reducing the mortality and clinical signs in DSS-induced acute colitis mice as compared to the untreated ones. We also found that IL-10 expression was induced in IL-19-treated colitis mice and prevented inflammatory infiltrates and proinflammatory cytokine expression in these mice. We suggest that S. choleraesuis encoding IL-19 provides a new strategy for treating IBD in the future.

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