背景与目的:细胞因子信号抑制因子(suppressor of cytokine signaling1,SOCS1)在肿瘤免疫负反馈调节中起重要作用,下调其表达可以有效增强机体的抗肿瘤免疫反应。本研究应用RNA干扰(RNA interference,RNAi)技术下调SOCS1基因表达联合OK-...背景与目的:细胞因子信号抑制因子(suppressor of cytokine signaling1,SOCS1)在肿瘤免疫负反馈调节中起重要作用,下调其表达可以有效增强机体的抗肿瘤免疫反应。本研究应用RNA干扰(RNA interference,RNAi)技术下调SOCS1基因表达联合OK-432刺激成熟的树突细胞(dendritic cell,DC)体外诱导特异性抗肿瘤作用,初步探讨其作用机制。方法:利用特异性小干扰RNA(siRNA)下调DC中SOCS1的表达,同时用肝癌HepG2细胞裂解物负载DC,OK-432刺激DC成熟,观察DC的形态特征,流式细胞仪检测刺激前后DC的表型变化,奥马蓝(AlamarBlue)法检测成熟DC对自身淋巴细胞的激活和增殖作用,LDH法检测其对HepG2、EC109细胞和K562细胞的杀伤作用。结果:DC体外诱导培养成功,设计的siRNA片段能有效下调iDC中SOCS1的表达,OK-432刺激DC成熟,CD80、CD83、CD86、HLA-DR等DC表面抗原明显表达上调,而负载肝癌抗原对DC表型无明显影响;SOCS1的下调可以促进DC成熟,负载肝癌抗原的DC能有效刺激自体淋巴细胞增殖,T细胞增殖率为(110.7±22.2)%,同时产生针对HepG2细胞的特异性杀伤作用,特异性细胞毒T淋巴细胞活性为(54.0±13.2)%。而针对EC109细胞和K562细胞的杀伤率仅为(10.0±30.7)%和(14.5±15.5)%。结论:RNAi下调SOCS1表达,OK432刺激负载肝癌全细胞抗原的成熟DC可以产生高效而特异性的抗肝癌的免疫应答。展开更多
HEp-2 cells persistently infected with respiratory syncytial virus(RSV) are a heterogeneous mixture of viral antigen-positive and-negative variants; however, the mechanism through which viral replication becomes laten...HEp-2 cells persistently infected with respiratory syncytial virus(RSV) are a heterogeneous mixture of viral antigen-positive and-negative variants; however, the mechanism through which viral replication becomes latent remains unclear. In this study, we investigated the potential mechanism by which RSV escapes from innate immune surveillance. Persistent-infected RSV HEp-2 cells were isolated and cell clones were passaged. The RSV-persistent cells produced viruses at a lower titer, resisted wild-type RSV re-infection, and secreted high levels of interferon-β(IFN-β), macrophage inflammatory protein-1α(Mip-1α), interleukin-8(IL-8), and Rantes. Toll-like receptor 3(TLR3), retinoic acid inducible gene-I(RIG-I), and suppressor of cytokine signaling 1(SOCS1) levels were upregulated in these cells. The silencing of TLR3 m RNA decreased the expression of SOCS1 protein and the secretion of cytokines. RSV-persistent cells are in an inflammatory state; upregulation of SOCS1 is related to the TLR3 signaling pathway, which could be associated with the mechanism of viral persistence.展开更多
目的研究信号转导和转录激活因子3(signal transducer and activator of transcription 3,STAT3)和细胞因子信号抑制因子3(suppressor of cytokine signaling 3,SOCS3)在中耳胆脂瘤中的表达及意义。方法采用免疫组织化学法检测30例中耳...目的研究信号转导和转录激活因子3(signal transducer and activator of transcription 3,STAT3)和细胞因子信号抑制因子3(suppressor of cytokine signaling 3,SOCS3)在中耳胆脂瘤中的表达及意义。方法采用免疫组织化学法检测30例中耳胆脂瘤标本与20例正常外耳道皮肤中STAT3及SOCS3蛋白的表达。结果STAT3蛋白阳性表达定位于胞浆和胞核,其在中耳胆脂瘤上皮中阳性表达率为76.7%(23/30),高于正常外耳道皮肤组的25.0%(5/20),差异有统计学意义(P<0.05);SOCS3蛋白阳性表达主要定位于胞浆,其在中耳胆脂瘤上皮的阳性表达率为33.3%(10/30),低于正常外耳道皮肤组的65.0%(13/20),差异有统计学意义(P<0.05);在30例中耳胆脂瘤上皮组织中,STAT3与SOCS3蛋白的表达呈负相关(r=-0.476,P=0.008,P<0.05)。结论STAT3和SOCS3蛋白在中耳胆脂瘤中的异常表达可能与中耳胆脂瘤上皮细胞的过度增殖和凋亡抑制相关,进而参与了胆脂瘤的发生发展。展开更多
类风湿关节炎是一种以滑膜炎症、骨质破坏、血管翳形成为特征的慢性对称性疾病。炎症介质与类风湿关节炎的发病机制关系密切,且随着炎症介质水平的升降,类风湿关节炎的严重程度明显受到影响。该文回顾了近年国内外学者对细胞因子信号转...类风湿关节炎是一种以滑膜炎症、骨质破坏、血管翳形成为特征的慢性对称性疾病。炎症介质与类风湿关节炎的发病机制关系密切,且随着炎症介质水平的升降,类风湿关节炎的严重程度明显受到影响。该文回顾了近年国内外学者对细胞因子信号转导抑制因子与类风湿关节炎的相关性研究,发现作为内源性负性调节因子,细胞因子信号转导抑制因子通过阻断信号转导和转录激活因子(signal transducer and activator of transcription,STAT)的磷酸化、抑制Janus激酶(Janus kinase,JAK)活性,参与细胞内外信号转导,介导T细胞存活和分化,诱导炎症因子的转录和激活,调控多种细胞因子的产生,对体内多种免疫反应的激活起调控作用。因此,作为抗炎的中介蛋白,细胞因子信号转导抑制因子通过多种途径参与炎症反应,与类风湿关节炎的发生发展密切相关,有望成为该病诊断和预后的生物标志物。同时,该文预测与细胞因子信号转导抑制因子相关的细胞凋亡、免疫调控、软骨代谢及自噬等相关性研究可能成为未来类风湿关节炎的研究热点。进一步深入探究细胞因子信号转导抑制因子与类风湿关节炎的相关性及其机制,可能为治疗类风湿关节炎开拓新视野。展开更多
The expression level of suppressor of cytokine signaling-3（SOCS-3） in human renal carcinoma and its methylation state were investigated. Reverse transcription-polymerase chain reaction（RT-PCR）, immuocytochemistry,...The expression level of suppressor of cytokine signaling-3（SOCS-3） in human renal carcinoma and its methylation state were investigated. Reverse transcription-polymerase chain reaction（RT-PCR）, immuocytochemistry, immunohistochemistry and Western blot were used to detect the expression level of SOCS-3, and the methylation of SOCS gene was investigated by methylation specific PCR in the tissues of 15 cases of renal carcinoma. Compared to those of the normal renal cell line and specimens , the expression level of SOCS-3 in renal carcinoma was significantly lower or can’t be detected（P0.01）. And the methylation of SOCS-3 gene in the tissue of renal carcinoma was significantly higher. The expression of SOCS-3 gene is significantly lower in renal carcinoma and the high methylation of the promoter island of SOCS-3 gene is associated with the lower expression of SOCS-3 gene. It may be one of main mechanisms for the development and progress of renal carcinoma.展开更多
基金supported by the National Natural Science Foundation of China (No. 81170005 and No. 30973220)
文摘HEp-2 cells persistently infected with respiratory syncytial virus(RSV) are a heterogeneous mixture of viral antigen-positive and-negative variants; however, the mechanism through which viral replication becomes latent remains unclear. In this study, we investigated the potential mechanism by which RSV escapes from innate immune surveillance. Persistent-infected RSV HEp-2 cells were isolated and cell clones were passaged. The RSV-persistent cells produced viruses at a lower titer, resisted wild-type RSV re-infection, and secreted high levels of interferon-β(IFN-β), macrophage inflammatory protein-1α(Mip-1α), interleukin-8(IL-8), and Rantes. Toll-like receptor 3(TLR3), retinoic acid inducible gene-I(RIG-I), and suppressor of cytokine signaling 1(SOCS1) levels were upregulated in these cells. The silencing of TLR3 m RNA decreased the expression of SOCS1 protein and the secretion of cytokines. RSV-persistent cells are in an inflammatory state; upregulation of SOCS1 is related to the TLR3 signaling pathway, which could be associated with the mechanism of viral persistence.
文摘目的研究信号转导和转录激活因子3(signal transducer and activator of transcription 3,STAT3)和细胞因子信号抑制因子3(suppressor of cytokine signaling 3,SOCS3)在中耳胆脂瘤中的表达及意义。方法采用免疫组织化学法检测30例中耳胆脂瘤标本与20例正常外耳道皮肤中STAT3及SOCS3蛋白的表达。结果STAT3蛋白阳性表达定位于胞浆和胞核,其在中耳胆脂瘤上皮中阳性表达率为76.7%(23/30),高于正常外耳道皮肤组的25.0%(5/20),差异有统计学意义(P<0.05);SOCS3蛋白阳性表达主要定位于胞浆,其在中耳胆脂瘤上皮的阳性表达率为33.3%(10/30),低于正常外耳道皮肤组的65.0%(13/20),差异有统计学意义(P<0.05);在30例中耳胆脂瘤上皮组织中,STAT3与SOCS3蛋白的表达呈负相关(r=-0.476,P=0.008,P<0.05)。结论STAT3和SOCS3蛋白在中耳胆脂瘤中的异常表达可能与中耳胆脂瘤上皮细胞的过度增殖和凋亡抑制相关,进而参与了胆脂瘤的发生发展。
文摘类风湿关节炎是一种以滑膜炎症、骨质破坏、血管翳形成为特征的慢性对称性疾病。炎症介质与类风湿关节炎的发病机制关系密切,且随着炎症介质水平的升降,类风湿关节炎的严重程度明显受到影响。该文回顾了近年国内外学者对细胞因子信号转导抑制因子与类风湿关节炎的相关性研究,发现作为内源性负性调节因子,细胞因子信号转导抑制因子通过阻断信号转导和转录激活因子(signal transducer and activator of transcription,STAT)的磷酸化、抑制Janus激酶(Janus kinase,JAK)活性,参与细胞内外信号转导,介导T细胞存活和分化,诱导炎症因子的转录和激活,调控多种细胞因子的产生,对体内多种免疫反应的激活起调控作用。因此,作为抗炎的中介蛋白,细胞因子信号转导抑制因子通过多种途径参与炎症反应,与类风湿关节炎的发生发展密切相关,有望成为该病诊断和预后的生物标志物。同时,该文预测与细胞因子信号转导抑制因子相关的细胞凋亡、免疫调控、软骨代谢及自噬等相关性研究可能成为未来类风湿关节炎的研究热点。进一步深入探究细胞因子信号转导抑制因子与类风湿关节炎的相关性及其机制,可能为治疗类风湿关节炎开拓新视野。
基金Supported by the Thirty-ninth Postdoctoral Science Foundation of China(No.20060390907)
文摘The expression level of suppressor of cytokine signaling-3（SOCS-3） in human renal carcinoma and its methylation state were investigated. Reverse transcription-polymerase chain reaction（RT-PCR）, immuocytochemistry, immunohistochemistry and Western blot were used to detect the expression level of SOCS-3, and the methylation of SOCS gene was investigated by methylation specific PCR in the tissues of 15 cases of renal carcinoma. Compared to those of the normal renal cell line and specimens , the expression level of SOCS-3 in renal carcinoma was significantly lower or can’t be detected（P0.01）. And the methylation of SOCS-3 gene in the tissue of renal carcinoma was significantly higher. The expression of SOCS-3 gene is significantly lower in renal carcinoma and the high methylation of the promoter island of SOCS-3 gene is associated with the lower expression of SOCS-3 gene. It may be one of main mechanisms for the development and progress of renal carcinoma.
