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1,25(OH)2 D3 inhibited Th17 cells differentiation via regulating the NF-?B activity and expression of IL-17.

ABSTRACT: OBJECTIVES:The role of vitamin D (VD) in innate and adaptive immune responses to tuberculosis is still unclear. Our research was aimed to uncover the effect of VD on Th17 cells and elucidate potential molecular mechanism. MATERIALS AND METHODS:VDR-deficient and wild-type mice were used to obtain CD4 T cells. Th17 cells were induced and activated by Bacillus Calmette Guerin. Flow cytometry was used to analyse the apoptosis rate and degree of differentiation of Th17 cells in the treatment of 1,25(OH)2 D3 . The interaction between P65 and Rorc was determined by immunofluorescence assay, luciferase reporter assay, EMSA-Super-shelf assay and ChIP assay. Co-IP assay was carried out to test the interaction between VDR and NF-?B family proteins. qRT-PCR and Western blot were also performed to detect the levels of P65, ROR?t and IL-17. RESULTS:The Th17 cells differentiation was suppressed by 1,25(OH)2 D3 in vitro. We confirmed that Rorc was a downstream gene of the transcription factor P65. VDR interacts with P105/P50, P100/P52 and P65 NF-?B family proteins. 1,25(OH)2 D3 inhibited the expression of ROR?t/IL-17 by suppressing p65 transcription factor translocating to nucleus. In vivo experiments, the expression of IL-17 and RANKL was suppressed by 1,25(OH)2 D3 by VD receptor. Moreover, 1,25(OH)2 D3 suppressed the inflammatory infiltrates and inhibited the expression of P65, ROR?t and IL-17 in the spleen tissues of model mice. CONCLUSIONS:Together, 1,25(OH)2 D3 suppressed the differentiation of Th17 cells via regulating the NF-?B activity.

SUBMITTER: Sun D

PROVIDER: S-EPMC6528876 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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1,25(OH)<sub>2</sub> D<sub>3</sub> inhibited Th17 cells differentiation via regulating the NF-κB activity and expression of IL-17.

Sun Dong D Luo Fei F Xing Jun-Chao JC Zhang Fei F Xu Jian-Zhong JZ Zhang Ze-Hua ZH

Cell proliferation 20180424 5

<h4>Objectives</h4>The role of vitamin D (VD) in innate and adaptive immune responses to tuberculosis is still unclear. Our research was aimed to uncover the effect of VD on Th17 cells and elucidate potential molecular mechanism.<h4>Materials and methods</h4>VDR-deficient and wild-type mice were used to obtain CD4 T cells. Th17 cells were induced and activated by Bacillus Calmette Guerin. Flow cytometry was used to analyse the apoptosis rate and degree of differentiation of Th17 cells in the tre ...[more]

PMID: 29687949

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Project description:Background and purposeThere is sufficient evidence to support vitamin D's noncalcemic effects and the role of vitamin D deficiency in the development of a wide range of neurological disorders. This study aimed to evaluate whether serum 25(OH)D and 1,25(OH) 2 D could be used as biomarkers to differentiate between healthy subjects (HS), multiple system atrophy (MSA) and Parkinson's disease (PD) patients of both genders.MethodsA total of 107 subjects were included in this study, divided into three groups: 1- HS (n = 61), 2- MSA patients (n = 19), and 3- PD patients (n = 27). The patients were assessed using UMSARS II, UPDRS III, H&Y, MMSE and MoCA rating scales. The levels of 25(OH)D and 1,25(OH) 2 D in serum were determined using the radioimmunoassay technique.ResultsThe levels of 25(OH)D and 1,25(OH) 2 D in HS were 26.85 +/- 7.62 ng/mL and 53.63 +/- 13.66 pg/mL respectively. 25(OH)D levels were lower in both MSA and PD by 61% and 50%, respectively (P = 0.0001 vs. HS). 1,25(OH) 2 D levels were lower in MSA by 29%(P = 0.001 vs HS). There was a correlation between 25(OH)D and 1,25(OH) 2 D in MSA and PD, but not in HS. 1,25(OH) 2 D regressed with MMSE (β = 0.476, P = 0.04, R 2 = 0.226) in MSA, and with UPDRS III (β = -0.432, P = 0.024, R 2 = 0.187) and MoCA (β = 0.582, P = 0.005,R 2 = 0.279) in PD. 25(OH)D displayed considerable differentiative strength between HS and MSA (Wald = 17.123, OR = 0.586, P = 0.0001; AUC = 0.982, sensitivity and Youden index = 0.882, P = 0.0001) and PD (Wald = 18.552, OR = 0.700, P = 0.0001; AUC = 0.943, sensitivity = 0.889, YI = 0.791, P = 0.0001). 1,25(OH) 2 D distinguished MSA from PD (Wald 16.178, OR = 1.117, P = 0.0001; AUC = 0.868, sensitivity = 0.926, Youden index =0.632, P = 0.0001). H&Y exhibited the highest sensitivity, AUC, and significant distinguishing power between MSA and PD.ConclusionsSerum 25(OH)D and 1,25(OH) 2 D could be useful biomarkers for MSA and PD. 25(OH)D and H&Y provided the highest sensitivity and group classification characteristics.

Project description:Chronic obstructive pulmonary disease (COPD), a major cause of morbidity and mortality worldwide, is widely considered to be related to cigarette smoke (CS), and viral infections trigger acute exacerbation of COPD (AECOPD). Isoforskolin (ISOF) is a bioactive component from the plant Coleus forskohlii, native to Yunnan in China. It has been demonstrated that ISOF has anti-inflammatory effect on acute lung injury animal models. In the present study, we investigated the efficacy and mechanism of ISOF for the prevention and treatment of AECOPD. Mice were exposed to CS for 18 weeks and then infected with influenza virus A/Puerto Rico/8/34 (H1N1). ISOF (0.5, 2 mg/kg) was intragastrically administered once a day after 8 weeks of exposure to cigarette smoke when the body weight and lung function of model mice declined significantly. The viral load, pulmonary function, lung morphology, Th17 cells, and inflammatory cytokines in lung tissues were evaluated. The expression of nuclear factor κB (NF-κB) and NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome pathways were detected. The results showed that ISOF treatment reduced the viral load in the lung homogenate, decreased the lung index of model mice, and lung pathological injuries were alleviated. ISOF also improved the pulmonary function with increased FEV0.1/FVC and decreased Rn and Rrs. The levels of inflammatory mediators (TNF-α, IL-1β, IL-6, IL-17A, MCP-1, MIG, IP-10, and CRP) in the lung homogenate were reduced after ISOF treatment. ISOF decreased the proportion of Th17 cells in the lung tissues by the flow cytometry test, and the protein expression levels of RORγt and p-STAT3 were also decreased. Furthermore, ISOF significantly inhibited the activation of NF-κB signaling and NLRP3 inflammasome in the lung tissues of model mice. In conclusion, ISOF alleviates AECOPD by improving pulmonary function and attenuating inflammation via the downregulation of proinflammatory cytokines, Th17/IL-17 A, and NF-κB/NLRP3 pathways.

Dataset Information

1,25(OH)2 D3 inhibited Th17 cells differentiation via regulating the NF-?B activity and expression of IL-17.

Publications

1,25(OH)<sub>2</sub> D<sub>3</sub> inhibited Th17 cells differentiation via regulating the NF-κB activity and expression of IL-17.

Similar Datasets

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