The Role Of Vitamin D Receptor In The Pathogenesis Of Myositis And The Intervention Effect Of Vitamin D On Myositis

Objective:We aimed to illustrate the effect of Vitamin D receptor (VDR) in the pathogenesis of myositis. With the treatment of Vitamin D, we observed the changes of vitamin D receptor, anti-inflammatory factors, pro-inflammatory factors and apoptosis related factors expressions in muscle tissue and serum of experimental autoimmune myositis animal model(EAM), exploring the pathogenesis of VDR and the preventive and therapeutic effects of VD.Methods:We used rabbit myosin, complete Freund’s adjuvant and pertussis toxin to produce EAM. We detected the levels of VDR, Foxp3, Granzyme B and CCR6mRNA in muscle tissue of myositis by use of PCR. We observed the changes of IL-4、IL-6、IL-8、IL-13、CD8、TNF-α、TGF-β1、IFN-γ、 Bcl-2and BAD expressions in muscle tissue of EAM by molecular biology methods. We also explored the pro-inflammatory factors (IL-6, IL-8, IL-17, IFN-γ, TNF-α), anti-inflammatory factors (IL-4, IL-10, IL-13, TGF-β), apoptosis related factors (BAD, BAX, Bcl-2), VD and VDR in blood of EAM by ELISA. Statistical analyses of the data were performed with the SPSS16.0software. The data were tested for deviations from normal distribution by Kolmogorov-Smirnov test and the nonparametric Mann-Whitney test was applied if data was not normally distributed. Correlation coefficients were calculated using Pearson’s rank method.Results:1, Our EAM induced by rabbit myosin, complete Freund’s adjuvant and pertussis toxin imitated muscle weakness and typical pathological changes of human myositis.2, VDR, Foxp3, GrB and CCR6mRNA expression in muscle tissue rised significantly in patients with myositis. But no obvious correlations were found between VDR expression and CCR6, Foxp3and GrB mRNA expressions, indicating VDR maybe take part in the pathogenesis of myositis alone.3, VDR was found to express in EAM compared with controls, and VD can enhance the expression of VDR protein, indicating VD could relieve the inflammation in muscle tissue by elevating the level of VDR. VD also can reduce the pro-inflammatory factors (IL-6, IFN-r and TNF-a) and raise the anti-inflammatory factors (IL-4, IL-10and TGF-β1) and Bcl-2, BAD mRNA to restrain the inflammation. VD could reduce the level of TGF-β1in the blood of EAM, but no effects were observed in the levels IL-6, IL-8, IL-17, IFN-γ, TNF-a, BAD, BAX, Bcl-2, VDR and VD.Conclusion:1, We produced ideal EAM on guinea pigs, which were induced by rabbit myosin, complete Freund’s adjuvant and pertussis toxin.2, VDR, CCR6, Foxp3, GrB all participated in the pathogenesis of myositis, but no correlations were found between them.3, VD may have preventive and therapeutic effects on myositis by elevating the expressions of VDR and anti-inflammatory factors and reducing pro-inflammatory factors.