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Eluted 25-hydroxyvitamin D3 from radially aligned nanofiber scaffolds enhances cathelicidin production while reducing inflammatory response in human immune system-engrafted mice.

ABSTRACT: Vitamin D3 modulates immune response, induces endogenous antimicrobial peptide production, and enhances innate immunity to defend against infections. These findings suggest that incorporating vitamin D3 into medical devices or scaffolds could positively modulate host immune response and prevent infections. In the current study, we evaluated host responses and endogenous antimicrobial peptide production using 25-hydroxyvitamin D3 (25(OH)D3)-eluting radially aligned PCL nanofiber scaffolds in human immune system-engrafted mice. We transformed traditional 2D electrospun nanofiber membranes into radially aligned PCL nanofiber scaffolds using the concept of solid of revolution and an innovative gas-foaming technique. Such scaffolds can promote rapid cellular infiltration and neovascularization. The infiltrating immune cells within subcutaneously implanted 25(OH)D3-containing scaffolds mainly consisted of human macrophages in the M1 phase (CCR7+), mice macrophages in the M2 phase (CD206+), and human cytotoxic T cells (CD8+) other than few human T-helper cells (CD4+). The 25(OH)D3-eluting nanofiber scaffolds significantly inhibited the production of pro-inflammatory cytokines (TNF-?, IL-6), while accelerating the production of anti-inflammatory cytokines (IL-4, IL-10) within the scaffolds. Additionally, we observed increased expression of human cathelicidin LL-37 within the 25(OH)D3-eluting scaffolds, while no LL-37 expression was observed in the control. Together, these findings support further work in the design of vitamin D3-eluting medical devices or scaffolds for modulating immune response and promoting antimicrobial peptide production. This could potentially reduce the inflammatory response, prevent infections, and eventually improve success rates of implants. STATEMENT OF SIGNIFICANCE: Transplant failure of medical devices, grafts, scaffolds, and tissue-engineered constructs due to inflammation and infection causes not only economic losses but also sufferings of second operation to the patient. Positive modulation of the host response to implants, scaffolds, and tissue-engineered constructs is likely to reduce the failure rate. Vitamin D3 plays an important role in modulating the immune response. It is able to not only reduce inflammation and induce endogenous antimicrobial peptide production but also prevent multidrug resistance and other side effects of traditional antibiotics. In this study, host responses to 25-hydroxyvitamin D3 (25(OH)D3)-eluting radially aligned PCL nanofiber scaffolds were evaluated in human immune system-engrafted mice. The 25(OH)D3-eluting medical devices or scaffolds were able to modulate positive immune response and promote antimicrobial peptide production. This work presented an innate immunity-enhancing approach for reducing the inflammatory response and preventing infections, likely resulting in improvement of success rates of implants.

SUBMITTER: Chen S

PROVIDER: S-EPMC6801031 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Eluted 25-hydroxyvitamin D3 from radially aligned nanofiber scaffolds enhances cathelicidin production while reducing inflammatory response in human immune system-engrafted mice.

Chen Shixuan S Ge Liangpeng L Wang Hongjun H Cheng Yan Y Gorantla Santhi S Poluektova Larisa Y LY Gombart Adrian F AF Xie Jingwei J

Acta biomaterialia 20190803

Vitamin D3 modulates immune response, induces endogenous antimicrobial peptide production, and enhances innate immunity to defend against infections. These findings suggest that incorporating vitamin D3 into medical devices or scaffolds could positively modulate host immune response and prevent infections. In the current study, we evaluated host responses and endogenous antimicrobial peptide production using 25-hydroxyvitamin D3 (25(OH)D3)-eluting radi ...[more]

PMID: 31386930

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Project description:Vitamin D signaling is important for intestinal homeostasis. An increase in vitamin D receptors in immune cells can modulate cell phenotype and cytokine secretion. Cytokines regulate both pro- (interleukin 17; IL-17) and anti-inflammatory (IL-10) responses triggered by external stimuli. Inflammation in intestinal tissues can disrupt the structure and the remodeling of epithelial tight junction complexes, thus, compromising the protective barrier. The objective of the study was to determine the impact of dietary supplementation with 25-hydroxycholecalciferol (25OHD3), a hydroxylated metabolite of vitamin D, on intestinal cytokine abundance and epithelial barrier integrity over time in broilers. A randomized complete block design experiment was conducted to evaluate the effect of dietary 25OHD3 inclusion on relative protein expression of the cytokines, IL-17 and IL-10, and tight junction proteins, Zona Occludens 1 (ZO-1), and Claudin-1 (CLD-1), in broiler chicken duodenum and ileum from 3 to 21 days post-hatch. On day 0, male chicks (n = 168) were randomly assigned to raised floor pens. Experimental corn-soybean meal-based treatments were as follows: (1) a common starter diet containing 5,000 IU of D3 per kg of feed (VITD3) and (2) a common starter diet containing 2,240 IU of D3 + 2,760 IU of 25OHD3 per kg of feed (25OHD3) fed from days 0 to 21. On days 3, 6, 9, 12, 15, 18, and 21, 12 birds per treatment were euthanized to collect tissue samples for quantitative, multiplex, and fluorescent Western blot analysis. Target proteins were quantified using Image Quant TL 8.1 and expressed relative to total protein. Feeding 25OHD3 post-hatch decreased ileal IL-10 (anti-inflammatory) protein expression in 21-day-old broilers compared with VITD3 only (P = 0.0190). Broilers fed only VITD3 post-hatch had greater IL-17 (pro-inflammatory) protein expression in the ileum at 18 and 21 days-of-age (P = 0.0412) than those that fed 25OHD3. Dietary inclusion of 25OHD3 lowered the abundance of key inflammatory cytokines in the ileum of young broilers.

Project description:Background and objectivesElevated concentrations of fibroblast growth factor 23 (FGF23) are postulated to promote 25-hydroxyvitamin D (25[OH]D) insufficiency in CKD by stimulating 24-hydroxylation of this metabolite, leading to its subsequent degradation; however, prospective human studies testing this relationship are lacking.Design, setting, participants, & measurementsAn open-label prospective study was conducted from October 2010 through July 2012 to compare the effect of 8 weeks of oral cholecalciferol therapy (50,000 IU twice weekly) on the production of 24,25(OH)2D3 in vitamin D-insufficient patients with CKD (n=15) and controls with normal kidney function (n=15). Vitamin D metabolites were comprehensively profiled at baseline and after treatment, along with FGF23 and other mineral metabolism parameters.ResultsVitamin D3 and 25(OH)D3 concentrations increased equivalently in the CKD and control groups following cholecalciferol treatment (median D3 change, 8.6 ng/ml [interquartile range, 3.9-25.6 ng/ml] for controls versus 12.6 ng/ml [6.9-41.2 ng/ml] for CKD [P=0.15]; 25(OH)D3 change, 39.2 ng/ml [30.9-47.2 ng/ml] for controls versus 39.9 ng/ml [31.5-44.1 ng/ml] for CKD [P=0.58]). Likewise, the absolute increase in 1α,25(OH)2D3 was similar between CKD participants and controls (change, 111.2 pg/ml [64.3-141.6 pg/ml] for controls versus 101.1 pg/ml [74.2-123.1 pg/ml] for CKD; P=0.38). Baseline and post-treatment 24,25(OH)2D3 concentrations were lower in the CKD group; moreover, the absolute increase in 24,25(OH)2D3 after therapy was markedly smaller in patients with CKD (change, 2.8 ng/ml [2.3-3.5 ng/ml] for controls versus 1.2 ng/ml [0.6-1.9 ng/ml] for patients with CKD; P<0.001). Furthermore, higher baseline FGF23 concentrations were associated with smaller increments in 24,25(OH)2D3 for individuals with CKD; this association was negated after adjustment for eGFR by multivariate analysis.ConclusionsPatients with CKD exhibit an altered ability to increase serum 24,25(OH)2D3 after cholecalciferol therapy, suggesting decreased 24-hydroxylase activity in CKD. The observed relationship between baseline FGF23 and increments in 24,25(OH)2D3 further refutes the idea that FGF23 directly contributes to 25(OH)D insufficiency in CKD through stimulation of 24-hydroxylase activity.

Dataset Information

Eluted 25-hydroxyvitamin D3 from radially aligned nanofiber scaffolds enhances cathelicidin production while reducing inflammatory response in human immune system-engrafted mice.

Publications

Eluted 25-hydroxyvitamin D<sub>3</sub> from radially aligned nanofiber scaffolds enhances cathelicidin production while reducing inflammatory response in human immune system-engrafted mice.

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