Organ-organ crosstalk is involved in homeostasis. Gastrointestinal symptoms are common in patients with renal failure. The aim of this study was to elucidate the relationship between gastrointestinal motility and gastrointestinal symptoms in chronic kidney disease. We performed studies in C57BL/6 mice with chronic kidney disease after 5/6 nephrectomy. Gastrointestinal motility was evaluated by assessing the ex vivo responses of ileum and distal colon strips to electrical field stimulation.Feces were collected from mice, and the composition of the gut microbiota was analyzed using 16S ribosomal RNA sequencing. Mice with chronic kidney disease after 5/6 nephrectomy showed a decreased amount of stool, and this constipation was correlated with a suppressed contraction response in ileum motility and decreased relaxation response in distal colon motility. Spermine, one of the uremic toxins, inhibited the contraction response in ileum motility, but four types of uremic toxins showed no effect on the relaxation response in distal colon motility. The 5/6 nephrectomy procedure disturbed the balance of the gut microbiota in the mice. The motility dysregulation and constipation were resolved by antibiotic treatments. The expression levels of interleukin 6, tumor necrosis factor-α, and iNOS in 5/6 nephrectomy mice were increased in the distal colon but not in the ileum. In addition, macrophage infiltration in 5/6 nephrectomy mice was increased in the distal colon but not in the ileum. We found that 5/6 nephrectomy altered gastrointestinal motility and caused constipation by changing the gut microbiota and causing colonic inflammation. These findings indicate that renal failure was remarkably associated with gastrointestinal dysregulation.

The cytokine interleukin-19 (IL-19) is a member of the IL-10 family that includes IL-20, IL-22, IL-24, and IL-26. Previous studies indicated that IL-19 is produced by keratinocytes, epithelial cells, macrophages, and B-cells. Especially, the number of IL-4-producing T cells increased, whereas the number of IFN-γ-producing T cells decreased when naive T cells from healthy people were cultured in the presence of IL-19. There is an increasing body of data demonstrating that IL-19 is associated with the development of type 1 helper T cell-responses, although IL-19 was originally associated with the development of type 2 helper T cell-responses. In this review, we will attempt to discuss current knowledge about the role of IL-19 on several T cell response-mediated inflammatory diseases including inflammatory bowel disease and hypersensitivity.

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Background: IL-19 is a member of the IL-10 family and produced by mainly macrophages, keratinocytes, epithelial cells, B cells, and vascular smooth muscle cells. However, little is known about the exact immunological role of IL-19 in the systemic inflammatory diseases in vivo. Inflammatory bowel disease results from chronic dysregulation of the mucosal immune system involving aberrant activation of innate and adaptive immune responses. Here, using gene-targeting, we have identified a novel role for IL-19 as a regulator in colonic inflammation. Methods: C57BL/6 genetic background IL-19 knockout (KO) mice were used. Mice received oral administration of dextran sodium sulfate (DSS), a sulfated polysaccharide that can disrupt the mucosal epithelial barrier, thereby exposing local macrophages to pathogenic stimuli from the intestinal microflora. The colitis was evaluated by analyzing mortality, the disease activity index (DAI), and histology of the distal colon. Clinical scores for weight loss, bleeding and diarrhea resulted in the DAI. Bone marrow-derived macrophages were cultured in vitro to determine cytokine production. Results: IL-19 KO mice showed severe mortality on administration of 3% DSS in drinking water for 7 days compared with wild-type (WT) mice. In accordance with the observed difference in survival, IL-19 KO mice showed much more severe weight loss. IL-19 KO mice had a significantly higher DAI score compared with WT mice on day 4 to day 8. Histological analysis revealed that the distal colons of IL-19 KO mice showed an increased number of infiltrating cells and a general loss of architecture, including extensive damage to both goblet and epithelial cells. The distal colon of IL-19 KO mice produced extremely high levels of IL-1beta, IL-6, IL-12, IFN-gamma, and TNF-alpha on day 5 after DSS administrations. Additionally the distal colon of IL-19 KO mice contained a high level of F4/80-pisitive cells. Bone marrow-derived macrophages from IL-19 KO mice produced significantly higher levels of IL-6, TNF-alpha and IL-12 than macrophages from WT mice following stimulation with LPS in vitro. Conclusions: Our findings indicate that IL-19 has previously undocumented roles in the protection of mucosal epithelial cells and the elimination of acute inflammation in the colon.