Serum 25-hydroxyvitamin D concentration is inversely associated with mucosal inflammation in patients with ulcerative colitis,

Meckel, Katherine; Li, Yan Chun; Lim, John; Kocherginsky, Masha; Weber, Christopher R.; Almoghrabi, Anas; Chen, Xindi; Kaboff, Austin; Sadiq, Farhana; Hanauer, Stephen B.; Cohen, Russell D.; Kwon, John H.; Rubin, David T.; Hanan, Ira M.; Sakuraba, Atsushi; Yen, Eugene F.; Bissonnette, Marc; Pekow, Joel

doi:10.3945/ajcn.115.123786

Cited by 82 publications

(68 citation statements)

References 53 publications

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“…Destruction of barrier function is found in colitis [29] . Our results showed that the expression levels of occludin and ZO-1 protein were significantly lower ( Figure 5C, 5D) in LPSinfected Caco-2 cells than in the control Caco-2 cells.…”

Section: Geniposide-induced Amelioration Of Barrier Dysfunction In Vitromentioning

confidence: 99%

Geniposide ameliorates TNBS-induced experimental colitis in rats via reducing inflammatory cytokine release and restoring impaired intestinal barrier function

et al. 2017

Acta Pharmacol Sin

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Geniposide is an iridoid glycosides purified from the fruit of Gardenia jasminoides Ellis, which is known to have antiinflammatory, antioxidative and anti-tumor activities. The present study aimed to investigate the effects of geniposide on experimental rat colitis and to reveal the related mechanisms. Experimental rat colitis was induced by rectal administration of a TNBS solution. The rats were treated with geniposide (25, 50 mg·kg, ig) or with sulfasalazine (SASP, 100 mg·kg, ig) as positive control for 14 consecutive days. A Caco-2 cell monolayer exposed to lipopolysaccharides (LPS) was used as an epithelial barrier dysfunction model. Transepithelial electrical resistance (TER) was measured to evaluate intestinal barrier function. In rats with TNBS-induced colitis, administration of geniposide or SASP significantly increased the TNBS-decreased body weight and ameliorated TNBS-induced experimental colitis and related symptoms. Geniposide or SASP suppressed inflammatory cytokine (TNF-α, IL-1β, and IL-6) release and neutrophil infiltration (myeloperoxidase activity) in the colon. In Caco-2 cells, geniposide (25-100 μg/mL) ameliorated LPS-induced endothelial barrier dysfunction via dose-dependently increasing transepithelial electrical resistance (TER). The results from both in vivo and in vitro studies revealed that geniposide down-regulated NF-κB, COX-2, iNOS and MLCK protein expression, up-regulated the expression of tight junction proteins (occludin and ZO-1), and facilitated AMPK phosphorylation. Both AMPK siRNA transfection and AMPK overexpression abrogated the geniposide-reduced MLCK protein expression, suggesting that geniposide ameliorated barrier dysfunction via AMPKmediated inhibition of the MLCK pathway. In conclusion, geniposide ameliorated TNBS-induced experimental rat colitis by both reducing inflammation and modulating the disrupted epithelial barrier function via activating the AMPK signaling pathway.

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Section: Geniposide-induced Amelioration Of Barrier Dysfunction In Vitromentioning

confidence: 99%

Geniposide ameliorates TNBS-induced experimental colitis in rats via reducing inflammatory cytokine release and restoring impaired intestinal barrier function

et al. 2017

Acta Pharmacol Sin

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“…In patients, serum vitamin D concentrations and UC disease activity are inversely related (42). The role of vitamin D in intestinal homeostasis has been shown through regulation of autophagy (43) and tight junctions (44).…”

Section: Resultsmentioning

confidence: 99%

Characterization of candidate genes in inflammatory bowel disease–associated risk loci

Peloquin¹,

Goel²,

Kong³

et al. 2016

JCI Insight

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GWAS have linked SNPs to risk of inflammatory bowel disease (IBD), but a systematic characterization of disease-associated genes has been lacking. Prior studies utilized microarrays that did not capture many genes encoded within risk loci or defined expression quantitative trait loci (eQTLs) using peripheral blood, which is not the target tissue in IBD. To address these gaps, we sought to characterize the expression of IBD-associated risk genes in disease-relevant tissues and in the setting of active IBD. Terminal ileal (TI) and colonic mucosal tissues were obtained from patients with Crohn’s disease or ulcerative colitis and from healthy controls. We developed a NanoString code set to profile 678 genes within IBD risk loci. A subset of patients and controls were genotyped for IBD-associated risk SNPs. Analyses included differential expression and variance analysis, weighted gene coexpression network analysis, and eQTL analysis. We identified 116 genes that discriminate between healthy TI and colon samples and uncovered patterns in variance of gene expression that highlight heterogeneity of disease. We identified 107 coexpressed gene pairs for which transcriptional regulation is either conserved or reversed in an inflammation-independent or -dependent manner. We demonstrate that on average approximately 60% of disease-associated genes are differentially expressed in inflamed tissue. Last, we identified eQTLs with either genotype-only effects on expression or an interaction effect between genotype and inflammation. Our data reinforce tissue specificity of expression in disease-associated candidate genes, highlight genes and gene pairs that are regulated in disease-relevant tissue and inflammation, and provide a foundation to advance the understanding of IBD pathogenesis.

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“…Elevated C-reactive protein as a marker of inflammation was inversely associated with 25(OH)D deficiency in newborns born in winter–spring, supporting this seasonal effect [63]. Moreover, dysbiosis of the microbiome and susceptibility to infection can be shaped by 25(OH)D status, further illustrating the biological importance of this molecule in maintaining health [64,65]. However, translating these findings to clinical trials of 1,25(OH) 2 D 3 supplementation in infants and adults have not been promising largely due to the inconsistency among trial designs.…”

Section: Discussionmentioning

confidence: 96%

Anti-Inflammatory Effects of Vitamin D on Human Immune Cells in the Context of Bacterial Infection

et al. 2016

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Vitamin D induces a diverse range of biological effects, including important functions in bone health, calcium homeostasis and, more recently, on immune function. The role of vitamin D during infection is of particular interest given data from epidemiological studies suggesting that vitamin D deficiency is associated with an increased risk of infection. Vitamin D has diverse immunomodulatory functions, although its role during bacterial infection remains unclear. In this study, we examined the effects of 1,25(OH)2D3, the active metabolite of vitamin D, on peripheral blood mononuclear cells (PBMCs) and purified immune cell subsets isolated from healthy adults following stimulation with the bacterial ligands heat-killed pneumococcal serotype 19F (HK19F) and lipopolysaccharide (LPS). We found that 1,25(OH)2D3 significantly reduced pro-inflammatory cytokines TNF-α, IFN-γ, and IL-1β as well as the chemokine IL-8 for both ligands (three- to 53-fold), while anti-inflammatory IL-10 was increased (two-fold, p = 0.016) in HK19F-stimulated monocytes. Levels of HK19F-specific IFN-γ were significantly higher (11.7-fold, p = 0.038) in vitamin D-insufficient adults (<50 nmol/L) compared to sufficient adults (>50 nmol/L). Vitamin D also shifted the pro-inflammatory/anti-inflammatory balance towards an anti-inflammatory phenotype and increased the CD14 expression on monocytes (p = 0.008) in response to LPS but not HK19F stimulation. These results suggest that 1,25(OH)2D3 may be an important regulator of the inflammatory response and supports further in vivo and clinical studies to confirm the potential benefits of vitamin D in this context.

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Serum 25-hydroxyvitamin D concentration is inversely associated with mucosal inflammation in patients with ulcerative colitis,

Cited by 82 publications

References 53 publications

Geniposide ameliorates TNBS-induced experimental colitis in rats via reducing inflammatory cytokine release and restoring impaired intestinal barrier function

Geniposide ameliorates TNBS-induced experimental colitis in rats via reducing inflammatory cytokine release and restoring impaired intestinal barrier function

Characterization of candidate genes in inflammatory bowel disease–associated risk loci

Anti-Inflammatory Effects of Vitamin D on Human Immune Cells in the Context of Bacterial Infection

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