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

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.

Early Growth Response Protein 1 Exacerbates Murine Inflammatory Bowel Disease by Transcriptional Activation of Matrix Metalloproteinase 12

“…Healthy control animals received water only. The clinical signs recorded in the colitis mice included survival, body weight, stool consistency, fecal bleeding, and diarrhea, as described previously [19].…”

“…These sections were stained with hematoxylin and eosin (H&E), and histological analysis was performed in a blinded fashion. Diarrhea score was evaluated as previously described [19].…”

“…AEC substrate solution (Zymed Laboratory, South San Francisco, CA, USA) was used as a substrate. The tissue sections were washed in PBS twice and counterstained with hematoxylin, as described previously [19].…”

“…Following homogenization, the samples underwent centrifugation at 16,000× g for 10 min at 4 • C to precipitate insoluble cellular debris, and the supernatant was stored at −80 • C until analysis. The concentrations of TNF-α, IL-6, and IL-1β will be evaluated using mouse ELISA kits (R&D Systems, Minneapolis, MN, USA), as described previously [19,20].…”