Institute of Microbiology and Immunology, Chung Shan Medical University, Taichung, Taiwan; Clinical Laboratory, Chung Shan Medical University Hospital, Taichung, Taiwan; Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan; Department of Healthcare Administration, Asia University, Taichung, Taiwan.
J Cell Mol Med. 2013 Oct;17(10):1308-15. doi: 10.1111/jcmm.12107. Epub 2013 Aug 2.
Attenuated antioxidant activities, irregular cytokines expressions and reduced regulatory T cells, are strongly associated with the pathogenesis of systemic lupus erythematosus (SLE). Despite the well-established beneficial effects of cystamine on lupus-prone mice, the extent to which cystamine contributes to antioxidant activity and the reduction of regulatory T cells has seldom been investigated. Therefore, this study elucidates how cystamine affects anti-oxidant activities in NZB/W F1 mice by performing assays of Glutathione (GSH), 1,1-diphenyl-2- picryl-hydrazyl (DPPH) and malondialdehyde thiobarbituric acid (MDA). In addition, investigations of the effects of cystamine on CD4(+) /CD25(+) regulatory T cells and interleukin-6 (IL6)/STAT-3 signalling were performed with flow cytometry and immunoblots. Experimental results reveal more significantly reduced MDA and increased GSH and DPPH in NZB/W F1 mice receiving cystamine than in those mice receiving PBS. Meanwhile, CD4(+) /CD25(+) regulatory T cells more significantly increase in NZB/W F1 mice receiving cystamine than in those mice receiving PBS, accompanied by significantly reduced IL-6/phosphorylated STAT-3 expression. The above findings suggest the beneficial effects of cystamine in terms of increasing antioxidant activities and CD4(+) /CD25(+) regulatory T cells in lupus-prone mice by suppressing IL-6/STAT3 signalling.
抗氧化活性减弱、细胞因子表达异常、调节性 T 细胞减少,与系统性红斑狼疮 (SLE) 的发病机制密切相关。尽管半胱胺对狼疮易感小鼠具有明确的有益作用,但半胱胺对抗氧化活性和调节性 T 细胞减少的影响程度很少被研究。因此,本研究通过测定谷胱甘肽 (GSH)、1,1-二苯基-2-苦基肼基 (DPPH) 和丙二醛硫代巴比妥酸 (MDA),阐明了半胱胺如何影响 NZB/W F1 小鼠的抗氧化活性。此外,还通过流式细胞术和免疫印迹法研究了半胱胺对 CD4(+) / CD25(+)调节性 T 细胞和白细胞介素 6 (IL6)/STAT-3 信号通路的影响。实验结果表明,与接受 PBS 的 NZB/W F1 小鼠相比,接受半胱胺的 NZB/W F1 小鼠的 MDA 明显降低,GSH 和 DPPH 明显增加。同时,接受半胱胺的 NZB/W F1 小鼠的 CD4(+) / CD25(+)调节性 T 细胞明显增加,而接受 PBS 的 NZB/W F1 小鼠的 CD4(+) / CD25(+)调节性 T 细胞明显减少,同时伴随 IL-6/磷酸化 STAT-3 表达明显减少。上述发现表明,半胱胺通过抑制 IL-6/STAT3 信号通路,增加狼疮易感小鼠的抗氧化活性和 CD4(+) / CD25(+)调节性 T 细胞,具有有益作用。