| Objective: Systemic lupus erythematosus(SLE)is a multifactorial autoimmune disease characterized by breakdown of self-tolerance,autoantibody production,aberrant formation of immune complexes(IC),and inflammation of multiple organs.Dendritic cells (DCs) are functionally abnormal in systemic lupus erythematosus (SLE). The present study was performed to identify a protective role for Xuebijing administration in systemic lupus erythematosus (SLE)-prone BLLF1 mice. To observe the effect of Xuebijing on DC to T lymphocyte and its potential mechanisms in SLE.Methods: A widely used model for in systemic lupus erythematosus (SLE)-prone BLLF1 mice was used in these studies. Ten normal female mice and thirty BLLF1 female mice were divided into four groups as follows: normal control group (10 mice), model control group (10 mice), SLE (8w) with Xuebijing treatment group (10 mice), and SLE(10w)Xuebijing treatment group (10 mice). Xuebijing 6.4ml/kg was given via dorsal penile vein in Xuebijing treatment group. In the first experiment,.animals of all groups were sacrificed, and blood, kidney samples were harvested aseptically to determine. In the second experiment spleen was divided into two parts as following: one part was used to procure DC by MACS microbeads and T cell by using column of nylon wool, and the other part was used to detect gene and protein expression levels of various cytokines. Cells were cultured and phenotypes were analyzed by flow cytometry. The contents of cytokines released into supernatants were also determined. Gene expression was measured by real-time quantitative PCR as the internal standard. All cytokines in supernatant and tissue were determined by ELISA kits for mice.Result: 1.Mice demonstrated characteristic alterations of serum immune parameters, the levels of anti-dsDNA antibodies in model control group were significantly higher than the normal group. Treatment with Xuebijing could inhibit the expression levels of anti-dsDNA antibodies.Conventional histological staining of kidneys showed abnormalities in BLLF1 mice at ages 8-10 weeks. Prominent mononuclear cell infiltrating was also observed, with predominantly perivascular localization in the cortex and medulla of the kidneys. In contrast, minimal histopathologic abnormalities can be observed in Xuebijing treatment group. The serum Crand CRE and BUN levels were significantly elevated in SLE, and treatment with Xuebijing could inhibit these increase to different extent.2.In the model control group, DC expressed strongly enhanced levels of CD80 and slightly enhanced levels of CD86 and MHC classⅡcompared with DC from normal mice. Treatment with Xuebijing could significantly up-regulated the expression levels of CD80, CD86 and MHC classⅡof DC. Splenic T lymphocyte proliferative response to ConA, were suppressed on days 3 and 5 after cultured in the presence of DC to T lymphocyte ratios in 1:100, 1:150 and 1:200 in the model control group, Xuebijing treatment could restore T cell proliferative activity. In the model control group, with marked production of interferon-γ, interleukin-2, TNF-alpha and interleukin-4 in supernatants, the levels of IL-4 and TNF-αincreased significantly ,but the levels of IL-2, and IFN-γand IL-12decreased markedly, The gene expression levels of IL-2 were also decreased and TNF-alpha were increased. Xuebijing treatment could significantly inhibite increase of IL-4, TNF-αand decrease of IL-2, IFN-γand IL-12.Conclusion: Dendritic cells play an important role in the development of SLE. The splenic DC express abnormally, and further induce suppression of T lymphocyte immune function and drifting to Th2 in SLE. Xuebijing treatment might influence the polarization of T cells in animals in SLE and induced Th cells to drift to Th1 cells. Xuebijihg has a potential therapeutic for suppressing immune dysfunction and ameliorating multiple organ injury in SLE. |
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