Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C1522057 (Colitis)
 3,500 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Reporter mice have been widely used to observe the localization of expression of targeted genes. This protocol focuses on a strategy to establish a new transgenic reporter mouse model. We chose to visualize interleukin (IL) 22 gene expression because this cytokine has important activities in the intestine, where it contributes to repair tissues damaged by inflammation. Reporter systems offer considerable advantages over other methods of identifying products in vivo. In the case of IL-22, other studies had first isolated cells from tissues and then re-stimulated the cells in vitro. IL-22, which is normally secreted, was trapped inside cells using a drug, and intracellular staining was used to visualize it. This method identifies cells capable of producing IL-22, but it does not determine whether they were doing so in vivo. The reporter design includes inserting a gene for a fluorescent protein (tdTomato) into the IL-22 gene in such a way that the fluorescent protein cannot be secreted and therefore remains trapped inside the producing cells in vivo. Fluorescent producers can then be visualized in tissue sections or by ex vivo analysis through flow cytometry. The actual construction process for the reporter included recombineering a bacterial artificial chromosome that contained the IL-22 gene. This engineered chromosome was then introduced into the mouse genome. Homeostatic IL-22 reporter expression was observed in different mouse tissues, including the spleen, thymus, lymph nodes, Peyer's patch, and intestine, by flow cytometry analysis. Colitis was induced by T-cell (CD4+CD45RBhigh) transfer, and reporter expression was visualized. Positive T cells were first present in the mesenteric lymph nodes, and then they accumulated inside the lamina propria of the distal small intestine and colon tissues. The strategy using BACs gave good-fidelity reporter expression compared to IL-22 expression, and it is simpler than knock-in procedures.
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PMID:Visualization of IL-22-expressing Lymphocytes Using Reporter Mice. 2819 33

Dietary nutrients have emerged as potential therapeutic adjuncts for inflammatory bowel disease (IBD) given their impact on intestinal homeostasis through the modulation of immune response, gut microbiota composition and epithelial barrier stability. Several nutrients have already been associated with a protective phenotype. Yet, there is a lack of knowledge toward the most promising ones as well as the most adequate phase of action. To unveil the most prominent therapy candidates we characterized the colon metabolic profile during colitis development. We have observed a twofold decrease in threonine levels in mice subjected to DSS-induced colitis. We then assessed the effect of threonine supplementation in the beginning of the inflammatory process (DSS + Thr) or when inflammation is already established (DSS + Thr D8). Colitis progression was similar between the treated groups and control colitic mice, yet threonine had a surprisingly detrimental effect when administered in the beginning of the disease, with mice displaying a delayed recovery when compared to control mice and mice supplemented with threonine after day 8. Although no major changes were found in their metabolic profile, DSS + Thr mice displayed altered expression in mucin-encoding genes, as well as in goblet cell counts, unveiling an impaired ability to produce mucus. Moreover, IL-22 secretion was decreased in DSS + Thr mice when compared to DSS + Thr D8 mice. Overall, these results suggest that supplementation with threonine during colitis induction impact goblet cell number and delays the recovery period. This reinforces the importance of a deeper understanding regarding threonine supplementation in IBD.
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PMID:L-Threonine Supplementation During Colitis Onset Delays Disease Recovery. 3023 16

The transcription factor Nkx2.3 regulates the vascular specification of Peyer patches in mice through determining endothelial addressin preference and may function as a susceptibility factor in inflammatory bowel diseases in humans. We wished to analyze the role of Nkx2.3 in colonic solitary intestinal lymphoid tissue composition and in colitis pathogenesis. We studied the colonic solitary intestinal lymphoid tissue of Nkx2.3-deficient mice with immunofluorescence and flow cytometry. Colitis was induced in mice using 2.5% dextran sodium sulfate, and severity was assessed with histology, flow cytometry, and quantitative PCR. We found that the lack of Nkx2.3 impairs maturation of isolated lymphoid follicles and attenuates dextran sodium sulfate-induced colitis independent of endothelial absence of mucosal addressin cell-adhesion molecule-1 (MAdCAM-1), which was also coupled with enhanced colonic epithelial regeneration. Although we observed increased numbers of group 3 innate lymphoid cells and Th17 cells and enhanced transcription of IL-22, Ab-mediated neutralization of IL-22 did not abolish the protection from colitis in Nkx2.3-deficient mice. Nkx2.3-/- hematopoietic cells could not rescue wild-type mice from colitis. Using LacZ-Nkx2.3 reporter mice, we found that Nkx2.3 expression was restricted to VAP-1+ myofibroblast-like pericryptal cells. These results hint at a previously unknown stromal role of Nkx2.3 as driver of colitis and indicate that Nkx2.3+ stromal cells play a role in epithelial cell homeostasis.
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PMID:IL-22-Independent Protection from Colitis in the Absence of Nkx2.3 Transcription Factor in Mice. 3070 May 85

Colitis, an inflammatory bowel disease, is caused by a variety of factors, but luminal microbiota are thought to play crucial roles in disease development and progression. Indole is produced by gut microbiota and is believed to protect the colon from inflammatory damage. In the current study, we investigated whether indole-3-carbinol (I3C), a naturally occurring plant product found in numerous cruciferous vegetables, can prevent colitis-associated microbial dysbiosis and attempted to identify the mechanisms. Treatment with I3C led to repressed colonic inflammation and prevention of microbial dysbiosis caused by colitis, increasing a subset of gram-positive bacteria known to produce butyrate. I3C was shown to increase production of butyrate, and when mice with colitis were treated with butyrate, there was reduced colonic inflammation accompanied by suppression of Th17 and induction of Tregs, protection of the mucus layer, and upregulation in Pparg expression. Additionally, IL-22 was increased only after I3C but not butyrate administration, and neutralization of IL-22 prevented the beneficial effects of I3C against colitis, as well as blocked I3C-mediated dysbiosis and butyrate induction. This study suggests that I3C attenuates colitis primarily through induction of IL-22, which leads to modulation of gut microbiota that promote antiinflammatory butyrate.
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PMID:Indole-3-carbinol prevents colitis and associated microbial dysbiosis in an IL-22-dependent manner. 3194 37