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杂色曲霉素对小鼠胸腺和脾脏转录因子Foxp3~+调节性T淋巴细胞的影响
Effect of sterigmatocystin on transcription factor Foxp3~+ regulatory T lymphocytes of thymus and spleen in mice
【摘要】 目的探讨杂色曲霉素(ST)对机体免疫调节功能的影响。方法BALB/c小鼠随机分为正常对照组、溶剂对照组、ST3,30,300和3000μg·kg-1组。小鼠ip给药24h后,处死取胸腺和脾脏,采用流式细胞术测定胸腺和脾脏细胞中CD4+和CD8+T淋巴细胞及转录因子Foxp3阳性(Foxp3+)调节性T淋巴细胞的百分率,免疫组织化学法检测胸腺和脾脏组织中Foxp3+调节性T淋巴细胞数量,Western蛋白印迹法和RT-PCR分别测定胸腺和脾脏组织中Foxp3蛋白和mRNA的表达。结果溶剂对照组与正常对照组比较,小鼠胸腺和脾脏CD4+,CD8+和Foxp3+T淋巴细胞百分率均无明显差异。与溶剂对照组比较,ST3μg·kg-1组胸腺CD8+T淋巴细胞百分率降低,ST3和30μg·kg-1组脾脏CD4+和CD8+T淋巴细胞百分率明显升高,ST300和3000μg·kg-1组胸腺和脾脏CD4+和CD8+T淋巴细胞百分率无明显变化。在ST3~3000μg·kg-1内,胸腺和脾脏细胞中Foxp3+调节性T淋巴细胞百分率、胸腺和脾脏组织内Foxp3+调节性T淋巴细胞数量、Foxp3蛋白和mRNA表达均随ST浓度的增高而增加。结论ST可诱导小鼠淋巴器官内Foxp3+调节性T淋巴细胞数量增加,从而影响机体免疫耐受功能。
【Abstract】 AIM To explore putative effects of sterigmatocystin (ST) on immunoregulatory function. METHODS BALB/c mice were randomly divided into normal control, solvent control and ST 3, 30, 300 and 3000 μg·kg-1 groups. The mice were sacrificed 24 h after ST was ip given and thymus and spleen were taken out. The percentages of CD4+ and CD8+ as well as transcription factor Foxp3+ regulatory T lymphocytes in thymus and spleen were determined with flow cytometric (FCM) method. The changes in number of Foxp3+ regulatory T cells were measured with immunohistochemical staining. Foxp3 expression at protein and mRNA level in thymus and spleen were respectively analyzed with Western blotting and reverse transcription polymerase chain reaction (RT-PCR) methods. RESULTS FCM results showed that there were no significant differences in the percentages of CD4+, CD8+ and Foxp3+ T in thymus and spleen between normal control and solvent control groups. Compared with control groups, the percentage of thymus CD8+ T cell in ST 3 μg·kg-1 group was significantly decreased, while that of splenic CD4+ and CD8+ T cells in both ST 3 and 30 μg·kg-1 groups were all significantly increased. No significant differences in the percentages of CD4+ or CD8+ T cells were found between ST 300 and 3000 μg·kg-1 groups with control groups in thymus and spleen. At the same time, the results revealed that from 3 to 3000 μg·kg-1, ST could significantly increase precentages and numbers of Foxp3+ T lymphocytes as well as expression of Foxp3 at both protein and mRNA levels in thymus and spleen dose-effectively. CONCLUSION ST exposure could induce increase in Foxp3+ regulatory T lymphocytes in lymphatic organ, thus may affect the immune tolerance of host.
【Key words】 sterigmatocystin; T-lymphocytes, regulatory; transcription factor; thymus; spleen;
- 【文献出处】 中国药理学与毒理学杂志 ,Chinese Journal of Pharmacology and Toxicology , 编辑部邮箱 ,2009年03期
- 【分类号】R379
- 【被引频次】11
- 【下载频次】162