Calcitriol analog ZK191784 ameliorates acute and chronic dextran sodium sulfate-induced colitis by modulation of intestinal dendritic cell numbers and phenotype

Strauch, Ulrike; Obermeier, Florian; Grunwald, Nicole; Dunger, Nadja; Rath, Heiko C.; Schölmerich, Jürgen; Steinmeyer, Andreas; Zügel, Ulrich; Herfarth, H.

doi:10.3748/wjg.v13.i48.6529

Cited by 17 publications

(7 citation statements)

References 37 publications

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“…It was speculated that this reduction was due to a direct suppressive effect on cytokine expression or the maintenance of epithelial barrier function, thus averting innate immune system activation [34]. Similar results were seen in two other studies examining the effects of Vitamin D analogs, ZK191784 and TX527, on TNF-α expression in DSS-induced colitis murine models [35,36].…”

Section: Tumor Necrosis Factor Alphasupporting

confidence: 60%

Effects of Vitamin D Supplementation on Inflammation, Colonic Cell Kinetics, and Microbiota in Colitis: A Review

et al. 2020

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Vitamin D is widely known to regulate bone health, but there is increasing evidence that it may also ameliorate colitis through inflammation, cell proliferation and apoptosis, and the microbiota. The purpose of this review is to systematically examine the mechanisms by which vitamin D reduces colitis. PubMed and Web of Science were searched for articles published between 2008 and 2019 using key words such as “vitamin D,” “colitis,” “inflammatory bowel disease,” “inflammation,” “apoptosis,” “cell proliferation,” and “gut bacteria”. Retrieved articles were further narrowed and it was determined whether their title and abstracts contained terminology pertaining to vitamin D in relation to colitis in human clinical trials, animal studies, and cell culture/biopsy studies, as well as selecting the best match sorting option in relation to the research question. In total, 30 studies met the established criteria. Studies consistently reported results showing that vitamin D supplementation can downregulate inflammatory pathways of COX-2, TNF-α, NF-κB, and MAPK, modify cell kinetics, and alter gut microbiome, all of which contribute to an improved state of colitis. Although vitamin D and vitamin D analogs have demonstrated positive effects against colitis, more randomized, controlled human clinical trials are needed to determine the value of vitamin D as a therapeutic agent in the treatment of colitis.

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Section: Tumor Necrosis Factor Alphasupporting

confidence: 60%

Effects of Vitamin D Supplementation on Inflammation, Colonic Cell Kinetics, and Microbiota in Colitis: A Review

et al. 2020

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“…Monoclonal anti-tumor necrosis factor α (TNF-α), currently used in therapy as infliximab, has been administered to dampen TNF-α mediated inflammation [43]; dexamethasone as a glucocorticoid receptor agonist [44]; statins acting in cholesterol checkpoint regulation of inflammation [45]; agonists of vitamin D3 as inducers of innate and adaptive regulatory function [46]; peroxisome proliferator-activated receptor gamma (PPAR-γ) agonists as repressing inflammatory transcriptional programs [47]; and IL-17A as mediating protection in T cell-mediated colitis [48], in addition to the many other monoclonal antibodies targeting components of the innate immune response. The administration of prebiotics/probiotics have also gained interest in their abilities to restore balance to the gastrointestinal microbiota and reduce intestinal inflammation, although whether or not these agents act as anti-inflammatory agents is yet to be clarified [49].…”

Section: Evidence Of Inflammation and Cancermentioning

confidence: 99%

Mechanisms of intestinal inflammation and development of associated cancers: Lessons learned from mouse models

Westbrook

Szakmary

Schiestl

2010

Mutation Research/Reviews in Mutation Research

101

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Chronic inflammation is strongly associated with approximately 1/5 th of all human cancers. Arising from combinations of factors such as environmental exposures, diet, inherited gene polymorphisms, infections, or from dysfunctions of the immune response, chronic inflammation begins as an attempt of the body to remove injurious stimuli; however, over time, this results in continuous tissue destruction and promotion and maintenance of carcinogenesis. Here we focus on intestinal inflammation and its associated cancers, a group of diseases on the rise and affecting millions of people worldwide. Intestinal inflammation can be widely grouped into inflammatory bowel diseases (ulcerative colitis and Crohn's disease) and celiac disease. Long-standing intestinal inflammation is associated with colorectal cancer and small-bowel adenocarcinoma, as well as extraintestinal manifestations, including lymphomas and autoimmune diseases. This article highlights potential mechanisms of pathogenesis in inflammatory bowel diseases and celiac disease, as well as those involved in the progression to associated cancers, most of which have been identified from studies utilizing mouse models of intestinal inflammation. Mouse models of intestinal inflammation can be widely grouped into chemically induced models; genetic models, which make up the bulk of the studied models; adoptive transfer models; and spontaneous models. Studies in these models have lead to the understanding that persistent antigen exposure in the intestinal lumen, in combination with loss of epithelial barrier function, and dysfunction and dysregulation of the innate and adaptive immune responses lead to chronic intestinal inflammation. Transcriptional changes in this environment leading to cell survival, hyperplasia, promotion of angiogenesis, persistent DNA damage, or insufficient repair of DNA damage due to an excess of proinflammatory mediators are then thought to lead to sustained malignant transformation. With regards to extraintestinal manifestations such as lymphoma, however, more suitable models are required to further investigate the complex and heterogeneous mechanisms that may be at play.

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“…It has been shown to exert therapeutic potential in T cell-mediated immune disorders and to significantly counteract acute and chronic intestinal inflammation [62]. While the 1,25(OH) 2 D 3 agonist effect of ZK191784 in kidney and antagonistic effect in intestine were clear, its effect on bone is still Ongoing: preliminay analyses appeared to suggest a tendency toward restoration of the reduced bone thickness in mice lacking the renal epithelial calcium channel TRPV (Trpv5 −/− ) [37].…”

Section: Vitamin D Deficiency and Supraphysiological Dosementioning

confidence: 99%

Vitamin D and Sphingolipids: Role in Bone and Neural System

Frati¹,

Gil²,

Pierucci³

et al. 2017

A Critical Evaluation of Vitamin D - Basic Overview

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Abstract1-Alpha,25-dihydroxyvitamin D3 (1,25(OH) 2 D 3 ) is known to play an important physiological role on growth and differentiation in a variety of nonmalignant and malignant cell types through classical actions, mediated by its specific receptor (VDR), and nongenomic actions resulting in the activation of specific signalling pathways. Due to the broad distribution of Vitamin D Receptor (VDR) in many tissues and the ability of 1,25(OH) 2 D 3 to regulate fundamental processes, such as cell proliferation and differentiation, this steroid hormone has been suggested in the treatment of different diseases, from cancer to neurodegenerative diseases. In fact, structural 1,25(OH) 2 D 3 analogues, with weaker collateral effects, have recently entered in clinical trials. Other interesting molecules due to their pleiotropic actions are the bioactive sphingolipids (SLs), in particular ceramide (Cer) and sphingosine 1-phosphate (S1P). Cells maintain a dynamic balance of these metabolites since Cer and sphingoid bases mediate cell death, while S1P exerts mitogenic effects and promotes differentiation of several cell types including osteogenic and neural cells. The biological actions of 1,25(OH) 2 D 3 and SLs, in particular S1P, share many common effectors, including calcium regulation, growth factor expression, inflammatory cytokines, etc., but whether they could act synergistically is still unknown and deserves further investigation.

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Calcitriol analog ZK191784 ameliorates acute and chronic dextran sodium sulfate-induced colitis by modulation of intestinal dendritic cell numbers and phenotype

Abstract: The calcitriol analog ZK191784 demonstrated significant anti-inflammatory properties in experimental colitis that were at least partially mediated by the immunosuppressive effects of the derivate on mucosal DCs.

Cited by 17 publications

References 37 publications

Effects of Vitamin D Supplementation on Inflammation, Colonic Cell Kinetics, and Microbiota in Colitis: A Review

Effects of Vitamin D Supplementation on Inflammation, Colonic Cell Kinetics, and Microbiota in Colitis: A Review

Mechanisms of intestinal inflammation and development of associated cancers: Lessons learned from mouse models

Vitamin D and Sphingolipids: Role in Bone and Neural System

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