ABSTRACT
Vitamin D3 is a kind of vitamin that plays important roles in maintaining the normal physiological function of the human body, and its metabolites and analogues exhibit strong anti-inflammatory activity. Vitamin D3 could be activated and converted into 1α, 25-dihydroxyvitamin D3, a kind of steroid hormone, in the human body, which participates in the regulation of cellular metabolism by activating vitamin D receptor (a kind of transcription factor), thus exerting immunomodulatory effects. This is essential for maintaining the physiological health of the body. Currently, there is a growing number of studies that suggest important roles for 1α, 25-dihydroxyvitamin D3 in organ transplantation immunomodulation and tolerance. Therefore, we reviewed the overview and physiological effects of 1α, 25-dihydroxyvitamin D3, the immunomodulatory effects of vitamin D3 and the application of vitamin D3 in clinical organ transplantation, and summarized the value of applying vitamin D3 in inducing immune tolerance in transplantation, with the aim of providing a reference for promoting the application of vitamin D3 in transplantation immunity.
ABSTRACT
Tumor cells along with a small proportion of cancer stem cells exist in a stromal microenvironment consisting of vasculature, cancer-associated fibroblasts, immune cells and extracellular components. Recent epidemiological and clinical studies strongly support that vitamin D supplementation is associated with reduced cancer risk and favorable prognosis. Experimental results suggest that vitamin D not only suppresses cancer cells, but also regulates tumor microenvironment to facilitate tumor repression. In this review, we have outlined the current knowledge on epidemiological studies and clinical trials of vitamin D. Notably, we summarized and discussed the anticancer action of vitamin D in cancer cells, cancer stem cells and stroma cells in tumor microenvironment, providing a better understanding of the role of vitamin D in cancer. We presently re-propose vitamin D to be a novel and economical anticancer agent.
ABSTRACT
Background:1 α,25-dihydroxyvitamin D3 [1,25 (OH) 2 D3],the active form of vitamin D,is reported in some studies having antifibrotic potential in liver fibrosis,however,its mechanism is not fully clarified.MicroRNAs (miRNAs) have recently been shown could regulate the proliferation and activation of hepatic stellate cells (HSCs),and are involved in the promotion or inhibition of liver fibrosis.Aims:To explore whether the inhibiting effect of 1,25 (OH) 2 D3 on activation of HSCs is by regulating miRNAs expression.Methods:Literature review and qPCR method were used to screen out the differentially expressed miRNAs between transforming growth factor-β1 (TGF-β1)-stimulated (activated) HSCs and the inactivated HSCs.Then the HSCs were co-cultured with TGF-β1 and the mimic of differentially expressed miRNA,the negative control mimic,1,25(OH)2D3 and DMSO,respectively,and the cell viability and apoptosis were determined by CCK-8 assay and flow cytometry.Results:Expression of miR-146a was down-regulated in activated HSCs (P ＜ 0.05).Compared with HSCs in DMSO group,the expression of miR-146a was significantly up-regulated in HSCs treated with 1,25 (OH) 2 D3;meanwhile,the cell viability was decreased and the apoptosis was increased (P all ＜ 0.05).In HSCs transfected with miR-146a mimic,the expression of miR-146a was up-regulated,the cell viability was decreased,and the apoptosis was increased similarly with HSCs in 1,25 (OH)2D3 group (P all ＜ 0.05).Conclusions:Regulation of miR-146a expression might be one of the important mechanisms of 1,25 (OH) 2 D3 in inhibiting TGF-β1-stimulated HSC activation and inducing apoptosis in HSCs.
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[ ABSTRACT] AIM:To evaluate the effects of 1α, 25-dihydroxyvitamin D3 on T helper cell 17 ( Th17 cells) and its related cytokines in a mouse model of corneal allograft transplantation.METHODS:C57BL/6 mice were transplanted with corneal grafts from BALB/c mice and treated intraperitoneally with 1.0μg 1α, 25-dihydroxyvitamin D3 or soybean oil every other day after operation.The transparency of the corneal grafts was evaluated for potential rejection signs by slit lamp biomicroscopy and histopathology.The expression levels of IL-17, RORγt and IFN-γin the spleen were measured by real-time PCR.Moreover, the protein expression of RORγt and IL-17 in the peripheral blood was analyzed by Western blotting. IL-17 and IFN-γin peripheral blood were measured by flow cytometry.RESULTS:1α, 25-dihydroxyvitamin D3 signifi-cantly inhibited the rejection of the corneal allograft and reduced the numbers of inflammatory infiltrates in the corneal graft. In the spleen, 1α, 25-dihydroxyvitamin D3 treatment reduced the expression levels of IL-17, RORγt and IFN-γ.In the pe-ripheral blood, 1α, 25-dihydroxyvitamin D3 treatment downregulated the expression levels of RORγt, IL-17 and IFN-γ. CONCLUSION:The effects of 1α, 25-dihydroxyvitamin D3 on suppressing corneal transplantation-induced allograft rejec-tion in mice are closely associated with its modulation on IL-17 and related cytokine RORγt.
ABSTRACT
Objective To establish a high-performance induction culture system for Raw264.7 cells to differentiate into osteoclasts(OC)invitro by improving the cell culture program.Methods The Raw264.7 cells were cultured withα-MEM medium containing 50 μg · L-1 M-CSF, 100 μg · L-1 RANKL, and 1 × 10-8 mol · L-1 1α,25-(OH)2 D3 in 5% CO2 for 12 d at 37℃. The cells were digested transiently every time before the medium was changed after every three days. The morphologic changes of the Raw264.7 cells were observed by inverted microscope.The maturation and phagotrophic function of OC were identified by HE,TRAP,FITC-phalloidin staining and immunofluorescence.Results The cells remained to grow in single layers all the time in most areas of the well during the whole induction by the improved culture program. The observation results of inverted microscope and HE staining showed that the growth area of the polykaryotic OC reached to 70% of the well on day 1 2. FITC-phalloidin staining showed that in the maturation of the OC, the cluster-shaped podosomes in the pseudopodia gradually transformed into rings,which finally fused to form a large belt surrounding the periphery of the cytoplasm. The calcitionin receptor (CTR) expressed by OC was markedly enhanced compared with the precursor cells by immunofluroescence staining,and a large number of red granules appeared in the cytoplasm of OC with TRAP staining on day 1 2. These results comfirmed that the obtained OC were maturated and owned phagotrophic function. Conclusion A high-performance induction culture system for Raw264. 7 cells to differentiate into OC in vitro induced by combination of 50μg · L-1 M-CSF, 100 μg · L-1 RANKL,and 1 × 10-8 mol·L-1 1α,25-(OH)2 D3 is established by improving the cell culture program.