Objective To observe if VIR576,an 20-mer peptide derived from the C-proximal subfragment of a1-antitrypsin(a1-AT)which inhibits human immunodeficiency virus type 1(HIV-1)entry into the target cells by interacting with...Objective To observe if VIR576,an 20-mer peptide derived from the C-proximal subfragment of a1-antitrypsin(a1-AT)which inhibits human immunodeficiency virus type 1(HIV-1)entry into the target cells by interacting with fusion peptide(FP),can also directly inhibit CD4^(+)T cell activation in vitro.Methods Splenocytes isolated from DO11.10 OVA Tg mice were stimulated with ovalbumin or concanavalin A to test the effects of VIR576 on antigen-specific or non-antigen-specific T cell activation.Both primary CD4^(+)CD25-T cells from DO11.10 mice and CD4^(+)T cell line A2b were activated with specific antigens to evaluate the effects of VIR576.Results VIR576 inhibited antigen-specific splenocyte activation but had no significant effect on non-antigen-specific T-cell activation,which bypassed the crosstalk between the CD3-signaling complex and TCR.We furthermore observed that VIR576 could also down-regulate antigen-specific CD4^(+)T-cell activation.Conclusion Given the high susceptibility of activated CD4^(+)T cells in the mucosa to HIV-1 infection,the inhibitory effects of VIR576 on both HIV entry into the target cells and CD4^(+)T-cell activation suggest the potential of VIR576 as a microbicide for prevention of sexual transmission of HIV.展开更多
目的:通过观察寿胎丸对体外小鼠Th1高分化的CD4+T细胞SOCS1和SOCS3蛋白表达的影响,探讨寿胎丸治疗反复自然流产的分子生物学机制。方法:以OVA及IL-12刺激CD4+T细胞,建立Th1高分化的CD4+T细胞模型,按药物浓度和作用时间的不同将细胞模型...目的:通过观察寿胎丸对体外小鼠Th1高分化的CD4+T细胞SOCS1和SOCS3蛋白表达的影响,探讨寿胎丸治疗反复自然流产的分子生物学机制。方法:以OVA及IL-12刺激CD4+T细胞,建立Th1高分化的CD4+T细胞模型,按药物浓度和作用时间的不同将细胞模型分为A、B两组,其中A组又分为空白血清对照组和寿胎丸低、中、高剂量药物血清组,B组分为0h、1h、2h、4h和8h组,W estern b lotting方法分别检测SOCS1和SOCS3蛋白的表达。结果:寿胎丸中剂量和高剂量药物血清可显著降低Th1高分化的CD4+T细胞SOCS1蛋白的表达(P<0.05),同时高剂量药物血清还可显著提高其SOCS3蛋白表达水平(P<0.05);寿胎丸高剂量药物血清分别作用2、4、8h均可显著降低SOCS1蛋白的表达(P<0.05),作用4h时达到最小值,高剂量药物血清分别作用2、4h可显著提高SOCS3蛋白表达水平(P<0.05),作用4h时达到最大值。结论:抑制Th细胞中SOCS1的表达和增加Th细胞中SOCS3的表达可能是寿胎丸治疗反复自然流产的分子生物学机制之一。展开更多
目的·探讨葡萄糖对小鼠CD4^+T细胞分化的影响。方法·小鼠初始CD4^+T细胞在调节性T细胞(regulatory T cell,Treg)、Th1、Th17和Th2分化条件下,经不同浓度的葡萄糖处理5 d后,利用流式细胞术检测细胞分化的比例,实时荧光定量PCR...目的·探讨葡萄糖对小鼠CD4^+T细胞分化的影响。方法·小鼠初始CD4^+T细胞在调节性T细胞(regulatory T cell,Treg)、Th1、Th17和Th2分化条件下,经不同浓度的葡萄糖处理5 d后,利用流式细胞术检测细胞分化的比例,实时荧光定量PCR检测相关细胞因子和转录因子的基因表达水平。结果·与无糖组相比,在Treg和Th2分化的条件下,随着葡萄糖浓度升高,Treg和Th2比例增高,其关键转录因子Foxp3(forkhead box P3)、Gata3(GATA binding protein 3)与主要细胞因子转化生长因子-β、白介素-4(interleukin-4,IL-4)和IL-13的基因水平增加;而随着葡萄糖浓度升高,Th1和Th17细胞比例则降低,其相关转录因子Tbx21(T-box transcription factor 21)和RORC(RAR related orphan receptor C),以及细胞因子干扰素-γ、IL-17A、IL-17F、IL-22和细胞因子受体IL-23R的基因表达下降。结论·葡萄糖能促进Treg和Th2体外分化,而抑制Th1与Th17分化。展开更多
基金Supported by National Natural Science Foundation of China(30672496 and 30801413)Guangdong Medical Research Grant(A201032)Guangdong International Cooperation Grant(2011B050200006)
文摘Objective To observe if VIR576,an 20-mer peptide derived from the C-proximal subfragment of a1-antitrypsin(a1-AT)which inhibits human immunodeficiency virus type 1(HIV-1)entry into the target cells by interacting with fusion peptide(FP),can also directly inhibit CD4^(+)T cell activation in vitro.Methods Splenocytes isolated from DO11.10 OVA Tg mice were stimulated with ovalbumin or concanavalin A to test the effects of VIR576 on antigen-specific or non-antigen-specific T cell activation.Both primary CD4^(+)CD25-T cells from DO11.10 mice and CD4^(+)T cell line A2b were activated with specific antigens to evaluate the effects of VIR576.Results VIR576 inhibited antigen-specific splenocyte activation but had no significant effect on non-antigen-specific T-cell activation,which bypassed the crosstalk between the CD3-signaling complex and TCR.We furthermore observed that VIR576 could also down-regulate antigen-specific CD4^(+)T-cell activation.Conclusion Given the high susceptibility of activated CD4^(+)T cells in the mucosa to HIV-1 infection,the inhibitory effects of VIR576 on both HIV entry into the target cells and CD4^(+)T-cell activation suggest the potential of VIR576 as a microbicide for prevention of sexual transmission of HIV.
文摘目的:通过观察寿胎丸对体外小鼠Th1高分化的CD4+T细胞SOCS1和SOCS3蛋白表达的影响,探讨寿胎丸治疗反复自然流产的分子生物学机制。方法:以OVA及IL-12刺激CD4+T细胞,建立Th1高分化的CD4+T细胞模型,按药物浓度和作用时间的不同将细胞模型分为A、B两组,其中A组又分为空白血清对照组和寿胎丸低、中、高剂量药物血清组,B组分为0h、1h、2h、4h和8h组,W estern b lotting方法分别检测SOCS1和SOCS3蛋白的表达。结果:寿胎丸中剂量和高剂量药物血清可显著降低Th1高分化的CD4+T细胞SOCS1蛋白的表达(P<0.05),同时高剂量药物血清还可显著提高其SOCS3蛋白表达水平(P<0.05);寿胎丸高剂量药物血清分别作用2、4、8h均可显著降低SOCS1蛋白的表达(P<0.05),作用4h时达到最小值,高剂量药物血清分别作用2、4h可显著提高SOCS3蛋白表达水平(P<0.05),作用4h时达到最大值。结论:抑制Th细胞中SOCS1的表达和增加Th细胞中SOCS3的表达可能是寿胎丸治疗反复自然流产的分子生物学机制之一。
