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| 1 | Expressions of Toll-like receptors 3,4,7,and 9 in cervical lesions and their correlation with HPV16 infection in Uighur women显示文摘Recent findings show that Toll-like receptors(TLRs) expressed in immune cells play a crucial role in the innate immune response and the subsequent induction of adaptive immune responses against microbial infection on tissue injury.Furthermore,expression of TLRs in cancer cells is associated with tumor proliferation and invasion.To explore the role of TLRs expression in cervical carcinogenesis in Uighur women,we detected the expressions of TLR3,TLR4,TLR7,and TLR9 in 25 normal cervical tissues,64 cervical intraepithelial neoplasia(CIN) tissues,and 63 cervical squamous cell carcinoma(CSCC) tissues using immunohistochemical staining,as well as human papillomavirus type 16(HPV16) infection using PCR.All samples used in this study were from Xinjiang Uighur women.We found the expression levels of TLR4,TLR7,and TLR9 were significantly higher in CIN and CSCC than in normal controls(P < 0.05).Up-regulation of TLR4 and TLR7 were correlated with tumor differentiation but not FIGO stage or lymph node metastasis(P > 0.05).Up-regulation of TLR9 was correlated with lymph node metastasis(P < 0.05) but not tumor differentiation or FIGO stage(P > 0.05).We also analyzed the correlation between the expressions of TLRs and HPV16 infection and found that the expressions of TLR4 and TLR9 significantly correlated with HPV16 infection in CIN(r = 7.434,P = 0.006;r = 7.123,P = 0.008) and CSCC(r = 6.423,P = 0.001;r = 8.478,P = 0.004),whereas the expression of TLR3 was not significantly different in any of the three groups and had no significant correlation with HPV16 infection.Our results suggest that high expression of TLR4,TLR7,and TLR9 may play important roles in the development and progression of CIN and CSCC in Uighur women,and the expressions of TLR4 and TLR9 can be up-regulated by HPV16 infection. | Ayshamgul Hasimu Lin Ge Qiao-Zhi Li Rui-Ping Zhang Xia Guo | 2011 | Chinese Journal of Cancer2011，30，5： | 26 |
| 2 | Plasmacytoid dendritic cells in antiviral immunity and autoimmunity显示文摘Plasmacytoid dendritic cells (pDCs) represent a unique and crucial immune cell population capable of producing large amounts of type I interferons (IFNs) in response to viral infection.The function of pDCs as the professional type I IFN-producing cells is linked to their selective expression of Toll-like receptor 7 (TLR7) and TLR9,which sense viral nucleic acids within the endosomal compartments.Type I IFNs produced by pDCs not only directly inhibit viral replication but also play an essential role in linking the innate and adaptive immune system.The aberrant activation of pDCs by self nucleic acids through TLR signaling and the ongoing production of type I IFNs do occur in some autoimmune diseases.Therefore,pDC may serve as an attractive target for therapeutic manipulations of the immune system to treat viral infectious diseases and autoimmune diseases. | TANG Fei1,2,DU Qiumei1,2 & LIU Yong-Jun3 1 Center for Infection and Immunity,Institute of Biophysics,Chinese Academy of Sciences,Beijing 100101,China 2 Graduate University of Chinese Academy of Sciences,Beijing 100049,China 3 Department of Immunology and Center for Cancer Immunology Research,University of Texas,M.D.Anderson Cancer Center,Houston,Texas 77030,USA | 2010 | Science China(Life Sciences)2010，53，2： | 23 |
| 3 | Overexpression of TLR3, TLR4, TLR7 and TLR9 in esophageal squamous cell carcinoma显示文摘AIM: To investigate the expression of Toll-like receptor (TLR) 3, TLR4, TLR7 and TLR9 in esophageal squamous cell carcinoma (ESCC). METHODS: Reverse transcription-polymerase chain reaction and immunohistochemistry were used to analyze the expression of TLR3, TLR4, TLR7 and TLR9 mRNA and protein in samples from 87 esophageal cancer patients consisting of both tumor and normal tissue. RESULTS: A significant increase in TLR3, TLR4, TLR7 and TLR9 mRNA levels was detected in ESCC samples. Tumors exhibited high TLR protein expression, (70.1%, 72.4%, 66.7% and 78.2% for TLR3, TLR4, TLR7 and TLR9, respectively, P < 0.05). Nevertheless, a significant percentage of tumors also exhibited TLR4 expression in mononuclear inflammatory cells (48.3%) and TLR9 expression in fibroblast-like cells (60.9%). Tumors with high TLR3 expression in tumor cells or high TLR4 expression in mononuclear inflammatory cells were significantly associated with a higher probability of lymph node metastasis and increased depth of invasion. However, tumors with high TLR9 expression in fibroblast-like cells were associated with low probabilities of invasion and metastasis. There was no significant variation between the expression of TLR3, TLR4, TLR7 and TLR9 among different ethnic groups. CONCLUSION: TLR3, TLR4, TLR7 and TLR9 expression appears important to the biological pathogenesis of ESCC. TLRs may represent therapeutic targets for ESCC. | Ilyar Sheyhidin Gulnaz Nabi Ayshamgul Hasim Rui-Ping Zhang Julaiti Ainiwaer Hong Ma Hua Wang | 2011 | World Journal of Gastroenterology2011，17，32： | 22 |
| 4 | Expression and Implication of Toll-like Receptors TLR2,TLR4 and TLR9 in Colonic Mucosa of Patients with Ulcerative Colitis显示文摘Toll-like receptors(TLRs) family may play important roles in inflammatory bowel disease. This study examined the expression of TLR2, TLR4 and TLR9 in the colonic tissues of patients with ulcerative colitis(UC) and explored their roles in the pathogenesis of UC. Colonic biopsies were taken from the colon of 30 patients with mild or moderate UC(at active phase) and 10 healthy controls during colonoscopy. TLR2, TLR4 and TLR9 protein expression levels were immunohistochemically detected. The mRNA expression levels of TLR2, TLR4 and TLR9 were assessed by reverse transcription polymerase chain reaction(RT-PCR). The disease activity index(DAI), colonoscopic and histologic grades and fecal microbial flora were determined. Histological examination showed that the intestinal mucous membrane of UC patients underwent acute inflammation changes. Immunohistochemistry exhibited that the expression levels of TLR2, TLR4 and TLR9 in colon epithelia and inflammatory cells were higher in UC patients than in control group(P<0.01). The mRNA expression levels of TLR2, TLR4 and TLR9 were increased in UC patients but were not detected in the normal controls. Expression levels of TLR2, TLR4 and TLR9 were positively correlated, and bore close correlation with DAI, colonoscopic and histologic grades and fecal microbial flora. An important mechanism of UC might be that abnormal activation of mucosal immunity by intestinal dysbacteriosis caused dysregulation of TLRS that mediates innate immunity. | 谭琰 邹开芳 钱伟 陈胜 侯晓华 | 2014 | Journal of Huazhong University of Science and Technology(Medical Sciences)2014，34，5： | 18 |
| 5 | TLR9在初发和复发尖锐湿疣皮损及外周血T细胞亚群中的表达显示文摘目的检测初发和复发尖锐湿疣(CA)患者皮损及外周血T细胞亚群中TLR9的表达情况,并探讨TLR9在HPV感染和CA复发机制中的作用。方法分别选用30例初发CA和27例复发CA患者皮损,并以28例正常人皮肤石蜡切片作为正常对照组。采用双色免疫荧光抗体染色流式细胞术检测入选者外周血T细胞中TLR9的表达。结果初发CA组和复发CA组皮损颗粒层和棘层TLR9表达(1.38±0.72和2.06±0.84)和外周血CD3+CD4+T细胞内TLR9表达[(11.4±3.2)%和(14.6±2.4)%]显著高于正常对照组[0.97±0.43和(6.2±2.1)%];另外,复发CA患者外周血CD3+CD4+T细胞内TLR9的表达也显著高于初发CA组;以上差异均有统计学意义(P均<0.05)。但是该两组患者的外周血CD3+CD8+T细胞内TLR9的表达与正常对照组差异不显著(P>0.05)。结论 CA皮损及外周血CD3+CD4+T细胞内TLR9表达上调可能是HPV病毒感染的识别受体,并参与机体的抗HPV免疫应答。TLR9可能在CA复发机制中发挥着重要的作用。 | 姜培红 李志豪 陈榕 房婕 | 2013 | 中国皮肤性病学杂志2013，27，2： | 17 |
| 6 | 基于TLR3/TLR9介导巨噬细胞自噬/极化效应探讨血管软化丸抗AS的作用机制显示文摘目的:观察血管软化丸通过对TLR3的影响,调控PI3K/Akt/mTOR信号通路,进而对巨噬细胞自噬产生影响,以及观察血管软化丸通过对TLR9的影响,调控下游NF-κB和IRF7信号途径,影响巨噬细胞M2/M1平衡,探讨血管软化丸抗动脉粥样硬化(AS)的分子机制。方法:体外实验,将巨噬细胞随机分为6组,即对照组(空白血清),血管软化丸高剂量组、血管软化丸中剂量组、血管软化丸低剂量组、ODN组(TLR9激动剂:ODN1826)、poly组(TLR3激动剂:poly(I:C))。体内实验,将ApoE^(-/-)小鼠分为6组,对照组(生理盐水,灌胃)血管软化丸高剂量组(浓度为3.456 g/mL),血管软化丸中剂量组(浓度为1.728 g/mL)、血管软化丸低剂量组(浓度为0.864 g/mL)、ODN组(ODN1826,腹腔注射)、poly组(poly(I:C),腹腔注射),腹腔注射每周两次,灌胃每日1次,连续给药8周后取材进行检测。观察血管软化丸含药血清和TLR9对巨噬细胞的极化状态的影响,对动脉斑块iNOS和CD206的表达的影响,对巨噬细胞(M1/M2)平衡相关炎症因子的影响和对巨噬细胞(M1/M2)平衡相关炎症因子的影响;采用ELISA法检测细胞分泌炎性因子相关水平,采用Western blot检测和RT-PCR法检测血管软化丸对主动脉斑块TLR9和TLR3及其下游信号分子表达的影响,观测指标:采用Western blot检测各组细胞TLR9的蛋白含量,及主动脉TLR9及其下游的分子MyD88,p-NF-κB和IRF7的蛋白含量;采用流式细胞术和免疫化学荧光检测各组细胞M1型和M2型的比例;采用RT-PCR和ELISA法检测各组细胞TNF-α的表达;采用RT-PCR和免疫荧光检测RAW264.7细胞和动脉斑块的M1型和M2型巨噬细胞的相关标志性因子和炎症因子;病理学检测验证血管软化丸抗动脉粥样硬化的疗效。结果:血管软化丸含药血清可以诱导巨噬细胞高表达M2型巨噬细胞的标志CD206;中药组斑块中iNOS的荧光密度表现为低表达(P<0.05),而斑块中CD206的荧光密度则表现为高表达(P<0.05);血管软化丸含药血清调低IL-1β、iNOS、Ciita表达(P<0.05),调高Ym1、Fizz1表达水平(P<0.05);能够改善细胞分泌炎性因子IFN-γ和IL-10相关水平(P<0.05);血管软化丸含药血清调低TLR9蛋白和TLR3蛋白表达水平(P<0.05);血管软化丸含药血清调低TLR9下游信号MyD88、p-NF-κB、IRF7 mRNA表达水平(P<0.05);血管软化丸含药血清调低TLR3下游信号LC3Ⅱ、Beclin、Akt、mTOR mRNA表达水平(P<0.05)。结论:血管软化丸通过影响TLR9,调控下游NF-κB和IRF7信号途径,进而调节巨噬细胞M2/M1平衡;通过调控TLR3影响PI3K/Akt/mTOR信号通路,进而调节巨噬细胞自噬,抑制动脉粥样硬化的发生发展。 | 秦合伟 李彦杰 任锟 张志鑫 赵晶 邢若星 韩磊 | 2019 | 辽宁中医杂志2019，46，1： | 15 |
| 7 | FoxP3、CD4^+CD25^+调节性T细胞、TLR2和TLR9在儿童传染性单核细胞增多症中的变化显示文摘本研究旨在探讨TLR2(Toll-like receptors,TLRs)、TLR9和CD4+CD25+调节性T细胞(Treg)及其转录因子FoxP3在儿童传染性单核细胞增多症(infectious mononucleosis,IM)发病中的作用。2010年4月至2011年1月我院儿科诊治的初次发病的急性期IM患儿35例(IM急性期组),IM恢复期组35例以及健康对照儿童35例(对照组)纳入研究。采用SYBR GreenⅠ实时荧光定量PCR方法检测外周血单个核细胞TLR2、TLR9、FoxP3mRNA的表达,运用流式细胞术检测外周血中T淋巴细胞亚群CD4+CD25+的表达。结果显示:IM急性期组TLR2mRNA(4.03±0.56)、TLR9 mRNA(8.88±1.56)相对表达水平显著高于对照组TLR2 mRNA(2.22±0.57)、TLR9mRNA(3.63±1.30)及恢复期组TLR2 mRNA(2.76±0.83)、TLR9 mRNA(5.34±1.60)相对表达水平(P<0.01)。IM急性期组FoxP3 mRNA(2.82±0.90)、CD4+CD25+(2.38±1.32%)表达水平显著低于对照组FoxP3mRNA(4.65±1.23)、CD4+CD25+(7.85±1.97%)及恢复期组FoxP3 mRNA(4.11±1.37)、CD4+CD25+(6.81±1.84%)(P<0.01),IM恢复期组FoxP3 mRNA、CD4+CD25+表达水平与对照组比较差异无统计学意义(P>0.05)。结论:IM急性期存在CD4+CD25+Treg数量降低及其特异性转录因子FoxP3表达下调,而TLR2和TLR9在IM急性期表达上调。 | 王强 王佐凤 曹玫 汪智英 | 2013 | 中国实验血液学杂志2013，21，2： | 14 |
| 8 | 变应性鼻炎患者血液嗜酸性粒细胞富集群中TLR2、TLR4、TLR7和TLR9的变化及其相关性显示文摘目的探讨变应性鼻炎(AR)患者血液嗜酸性粒细胞富集群中TLR2、TLR4、TLR7和TLR9的变化及其相关性,探索其在AR中的发病机制。方法收集健康人和AR患者的外周静脉血,用蒿草花粉、尘螨和梧桐花粉过敏原提取液刺激,流式细胞术检测刺激前后嗜酸性粒细胞富集群中TLR2、TLR4、TLR7和TLR9的表达,SPSS软件分析TLR2^+、TLR4^+、TLR7^+和TLR9^+嗜酸性粒细胞的相关性。结果与健康组比较,AR患者未经过敏原刺激时嗜酸性粒细胞富集群中TLR2^+细胞的比例降低4%,TLR4^+细胞的平均荧光强度(mean fluorescence intensity,MFI)升高20%,TLR7^+细胞的比例升高4.8倍。蒿草花粉过敏原提取液诱导AR患者TLR2^+嗜酸性粒细胞的比例升高7.8%。此外,AR患者血液TLR2^+和TLR4^+、TLR2^+和TLR7^+、TLR7^+和TLR9^+的嗜酸性粒细胞均呈中度相关(Pearson相关系数分别为r=-0.670,P<0.01;r=-0.430,P<0.05;r=0.446,P<0.05)。而健康人嗜酸性粒细胞富集群中TLR2、TLR4、TLR7和TLR9的变化在过敏原刺激前后差异均无统计学意义。结论嗜酸性粒细胞源的TLR2、TLR4和TLR7可能在AR中起重要作用,TLR2、TLR4和TLR7可能是治疗AR的潜在靶点。 | 张晓文 张慧云 王维 湛萌萌 何韶衡 | 2018 | 西安交通大学学报(医学版)2018，39，4： | 14 |
| 9 | Toll样受体9和核因子-κBp65在大鼠溃疡性结肠炎模型结肠组织中的表达及其相关性的研究显示文摘目的观察Toll样受体9(TLR9)、核因子-κBp65(NF-κBp65)在溃疡性结肠炎(ulcerativecolitis,UC)大鼠模型结肠粘膜中的表达情况,探讨二者在UC发病机制中的作用及其相关性。方法运用复合法(2,4-二硝基氯苯+乙酸)制备细胞免疫反应性UC大鼠模型,造模成功后,观察和评估结肠黏膜的大体形态和组织学变化;应用免疫组化Elivision法检测UC模型组和正常对照组大鼠结肠粘膜中TLR9和NF-κBp65表达,并分析其与病理组织学分级的关系。结果UC大鼠结肠粘膜中TLR9阳性表达率明显高于正常对照(P〈0.01)。在UC大鼠结肠粘膜组织学分级I、Ⅱ、Ⅲ级中的TLR9表达分别为13.75±9.78、49.33±17.76、82.4±29.46。表达的TLR9也存在显著差异,其中TLR9在I级与Ⅲ级UC大鼠中的表达有显著差异(P〈0.01),而Ⅱ级与Ⅰ级、Ⅱ级与Ⅲ级UC大鼠表达的TLR9也存在显著差异(P〈0.05)。NF-κB;p65在UC大鼠结肠粘膜中的阳性表达率明显高于正常对照组(P〈0.01)。在UC组织学分级为Ⅰ、Ⅱ、Ⅲ级的三组大鼠结肠粘膜中,NF-κBp65的表达分别为8.75±7.18、41.83±11.99、68.4±26.76。其中,I级与Ⅲ级UC大鼠相比,NF-κBp65的表达有极显著差异(P〈0.01),比较Ⅱ级与Ⅰ级、Ⅱ级与Ⅲ级UC大鼠NF-κBp65的表达也有显著差异(P〈0.05)。UC大鼠结肠粘膜中TLR9表达与NF-κBp65表达呈显著正相关(rs=0.971,P〈0.01)。结论UC大鼠结肠粘膜中TLR9、NF-κBp65表达明显升高,且与疾病的组织学分级呈正相关,提示其可能与UC的发生、发展有关。TLR9和NF-κBp65在UC结肠粘膜中的表达呈显著正相关,表明NF-κBp65是TLR9信号通路活化的产物。 | 何雁 王启之 燕善军 汪强武 李大鹏 于东红 | 2011 | 国际免疫学杂志2011，34，6： | 13 |
| 10 | TLR9免疫识别CpG DNA的机制与途径显示文摘Toll样受体介导的信号转导通路在对抗外来病原微生物的天然免疫应答中起重要作用。新发现的Toll样受体 9(TLR9)是哺乳动物识别细菌DNA中非甲基化的胞嘧啶 磷酸 鸟嘌呤基序 (CpGDNA)的主要受体。经典的信号转导途径如NF κB活化通路 ,MAPK通路在对CpGDNA的应答中均被启动。 | 李宁 范学工 | 2003 | 国外医学(分子生物学分册)2003，25，5： | 11 |
| 11 | Effects of CPG ODN on biological behavior of PANC-1 and expression of TLR9 in pancreatic cancer显示文摘AIM:To determine the expression of toll-like receptor 9(TLR9) in pancreatic tumor and the effects of cytosine phosphate-guanosine oligodeoxynucleotides 2216(CPG ODN2216) on biological behavior of pancreatic carcinoma cell line PANC-1 and explore their clinical significance.METHODS:The immunohistochemistry and Western blot were used to determine the expression of TLR9 protein in pancreatic cancer tissues,and immunofluorescence staining was performed to detect the TLR9 protein expression in pancreatic carcinoma cell line PANC-1.To assess the effects of CPG ODN2216 on the invasive property of Panc-1 cells,in vitro cell adhesion,wound-healing scrape,and invasion and cell colony formation were evaluated.RESULTS:TLR9 was highly expressed in pancreaticcancer tissues and PANC-1 cells.The percentage of positive cells expressing TLR9 protein in human pancreatic tissues,paracancerous tissues and normal tissues were 73.3%,33.3% and 20.0%,respectively,and the protein expression level of TLR9 was gradually descending(P < 0.05).In vitro tests in wound-healing scrape,cell adhesion,colony formation and matrigel invasion showed that the adhesion and motility of PANC-1 cells in CPG ODN 2216 treatment group were signif icantly lower than in the control group(P < 0.05).The cell growth assay showed that the proliferative ability of PANC-1 cells in treatment group was significantly decreased and CPG ODN2216 had an inhibitive effect in the growth of Panc-1 cells in a dose and time-dependent manner(P < 0.05).CONCLUSION:The gene of TLR9 is correlated with the invasive and metastatic potential of human pancreatic carcinoma,and CPG ODN2216 induces the inhibition of migration and invasion of Panc-1 cells. | Han-Qing Wu Bo Wang Shi-Kai Zhu Yuan Tian Jing-Hui Zhang He-Shui Wu | 2011 | World Journal of Gastroenterology2011，17，8： | 10 |
| 12 | TLR2、TLR9及T细胞亚群在传染性单核细胞增多症患儿中的变化及意义显示文摘目的本研究旨在探讨Toll样受体(TLR)2、TLR9及T细胞亚群在传染性单核细胞增多症(IM)患儿中的变化及意义。方法研究对象为2010年4月-2011年1月我院儿科初治急性期IM患儿35例(IM急性期组),IM恢复期组35例以及健康对照儿童35例(对照组)。采用SYBR GreenⅠ实时荧光定量PCR方法检测外周血单个核细胞TLR2 mRNA、TLR9 mRNA的表达,运用流式细胞术检测外周血中CD3+、CD3+CD4+、CD3+CD8+、CD4+CD25+T细胞的阳性表达率。结果 (1)IM急性期组TLR2mRNA(4.03±0.56)、TLR9mRNA(8.88±1.56)相对表达水平显著高于对照组TLR2mRNA(2.22±0.57),TLR9mRNA(3.63±1.30)及恢复期组TLR2mRNA(2.76±0.83),TLR9mRNA(5.34±1.60)(P<0.01)。(2)IM急性期组CD3+、CD3+CD4+、CD3+CD8+、CD4+/CD8+、CD4+CD25+细胞百分比分别为(80.66±4.88)%、(16.53±5.55)%、(62.71±8.76)%、0.26±0.12、(2.38±1.32)%,对照组分别为(63.04±5.51)%、(37.98±4.20)%、(27.71±6.52)%、1.37±0.45、(7.85±1.97)%,二者之间差异有显著性(P<0.01);IM恢复期组儿童CD3+、CD3+CD4+、CD3+CD8+、CD4+/CD8+、CD4+CD25+细胞百分比分别为(74.25±7.33)%、(29.89±6.03)%、(42.25±7.33)%、0.71±0.19、(6.81±1.84)%,与IM急性期组比较差异有显著性(P<0.01),IM恢复期组CD4+CD25+细胞百分比与对照组[(7.85±1.97)%]比较差异无显著性(P>0.05)。结论 (1)IM急性期TLR2mRNA、TLR9mRNA表达相对上调,而IM恢复期二者表达相对下调;(2)IM急性期存在明显的免疫失衡,即CD3+CD8+明显增高,CD3+CD4+、CD4+/CD8+及CD4+CD25+Treg明显降低。提示在IM病程不同时期TLR2与TLR9的改变可能通过对T细胞的调节参与了IM发病。 | 王强 王佐凤 曹玫 汪智英 | 2013 | 中国小儿血液与肿瘤杂志2013，18，6： | 10 |
| 13 | 大黄素对重症急性胰腺炎肺损伤大鼠胰腺及肺组织Toll样受体4和9表达的影响显示文摘目的:研究Toll样受体TLR4和TLR9在重症急性胰腺炎(SAP)肺损伤中的表达及大黄素(EMO)对其的影响。方法:56只大鼠随机分为3组,模型组、EMO组各24只及假手术组8只。模型组和EMO组采用开腹胰胆管逆行注射3.5%牛磺胆酸钠建立SAP肺损伤模型,假手术组以开腹轻微翻动胰腺即关腹代替;EMO组在术前、术后1h按10ml/kg体重腹腔注射4mg/ml浓度的EMO混悬液,假手术组和模型组大鼠以注射4%蔗糖脂肪酸酯混悬液代替,假手术组术后3h后处理,模型组和EMO组于术后3h、6h、12h分批处理8只;采用免疫组化检测胰腺和肺组织TLR4、TLR9和核转录因子κB(NF-κB)蛋白表达。结果:与假手术组比,模型组除肺组织术后3h的TLR4、TLR9、NF-κB以及6h的TLR9外,其余各时间点胰腺及肺组织TLR4、TLR9和NF-κB表达均显著增高(P<0.05,P<0.01);6h时间点,EMO组胰腺、肺组织TLR4、NF-κB以及胰腺TLR9表达均较模型组明显上调(P<0.05);12h时间点,EMO组胰腺及肺组织TLR4、TLR9、NF-κB表达较模型组表达明显下调(P<0.05)。结论:TLR4和TLR9在SAP大鼠肺损伤中有重要作用;EMO防治SAP肺损伤的机制可能与其调节胰腺和肺组织中TLR4和TLR9的表达有关。 | 蔡丹莉 高凯 陈芝芸 石占利 徐华 朱渊红 戴显微 | 2018 | 浙江中医杂志2018，53，12： | 9 |
| 14 | TLR9,先天免疫中重要的抗微生物受体显示文摘先天免疫系统是宿主抵御外来微生物入侵的第一道防线,TLR9是先天免疫系统中识别细菌和病毒CpG DNA的主要受体。TLR9信号转导利用MyD88依赖途径,在IRAK-4、IRAK-1、TRAF6和TAK1等关键信号蛋白的协同作用下,激活NF-κB和MAP途径,诱导产生一系列促炎细胞因子和趋化因子,最终引起Th1样炎症反应。TLR9除了有抗感染作用,还与自身免疫紊乱和一些恶性肿瘤发生相关。研究TLR9能帮助了解相关疾病发病机理及寻求预防和治疗的手段。 | 黄巧茹 | 2007 | 中山大学研究生学刊(自然科学与医学版)2007，28，3： | 8 |
| 15 | TLR9在人鼻黏膜上皮细胞中的表达及意义显示文摘目的:利用RT-PCR、免疫组织化学及流式细胞术检测原代培养的人鼻黏膜上皮细胞TLR9的表达水平及意义。方法:原代培养人鼻黏膜上皮细胞,设计TLR9的引物,RT-PCR检测TLR9 mRNA在鼻黏膜上皮细胞中的表达。免疫组织化学及流式细胞术检测原代培养的人鼻黏膜上皮细胞中TLR9的表达水平。结果:400倍光镜下观察结果显示,原代培养的鼻黏膜上皮细胞呈圆形或不规则形,饱满贴壁。RT-PCR结果显示,鼻黏膜上皮细胞有TLR9 mRNA的表达。通过与内参照物GAPDH进行灰度分析比较,发现鼻黏膜上皮细胞中TLR9的表达高于外周血单个核细胞阳性对照组,差异有统计学意义。结论:人鼻黏膜上皮细胞中有TLR9的表达,TLR9 mRNA在人鼻黏膜上皮细胞中的表达高于外周血单个核细胞。 | 朱学伟 朱冬冬 董震 孙克巍 | 2008 | 临床耳鼻咽喉头颈外科杂志2008，22，8： | 7 |
| 16 | 灵猫方联合替比夫定治疗慢性乙型肝炎患者的疗效及对NK细胞功能的影响显示文摘目的:观察灵猫方联合替比夫定治疗慢性乙型肝炎(CHB)患者的临床疗效及其对患者外周血自然杀伤细胞(NK)数量、功能的影响,探讨灵猫方治疗CHB的免疫调节机制。方法:纳入54例符合标准的CHB患者,随机分为单用组27例和联合组27例,同时纳入10例健康志愿者作为健康对照组。两组均给予口服替比夫定治疗,联合组加服灵猫方,疗程为24周。治疗3个月、6个月时,评价两组患者的中医证候积分,检测两组患者的谷丙转氨酶(ALT)、谷草转氨酶(AST)、HBV-DNA定量、HbeAg、外周血NK细胞数量及细胞表面和胞内Toll样受体(TLRs)的表达水平,比较两组患者的ALT、AST复常率,HBV-DNA阴转率和HBeAg血清转换率。结果:治疗3个月、6个月后,两组患者的中医证候积分较治疗前均显著降低(P<0.05,P<0.01),且联合组患者的中医证候积分明显低于单用组(P<0.01)。治疗3个月、6个月后,两组患者的ALT、AST水平均显著降低(P<0.01),且治疗3个月时,联合组患者的ALT、AST水平低于单用组(P<0.05),ALT、AST复常率明显高于单用组(P<0.05)。治疗3个月、6个月后,两组患者的HBVDNA、HBeAg水平均明显降低(P<0.01),但两组患者的HBV-DNA转阴率、HBeAg血清转换率比较,差异无统计学意义(P>0.05)。与健康对照组比较,CHB患者的外周血NK细胞数量明显减少(P<0.05),NK细胞胞内TLR3、TLR9表达水平显著降低(P<0.05);治疗3个月、6个月后,两组患者的NK细胞数量及胞内、胞外TLR3、TLR9表达水平较治疗前均明显提高(P<0.05),且联合组患者NK细胞数量及其胞内TLR3表达水平明显高于单用组(P<0.05)。结论:灵猫方联合替比夫定可显著改善CHB患者的中医证候和肝功能,灵猫方的作用机制可能与提高患者的NK细胞数量及其胞内外TLR3的表达水平,从而调节机体的免疫功能有关。 | 江云 高月求 李曼 张鑫 周振华 | 2017 | 上海中医药大学学报2017，31，2： | 7 |
| 17 | IFN-a production by human mononuclear cells infected with varicella-zoster virus through TLR9-dependent and-independent pathways显示文摘Understanding the defense mechanisms of the host of an organism is important for infection control.In previous studies,we demonstrated that interferon-a(IFN-a),but not IL-12,was produced by human peripheral blood mononuclear cells infected with varicella-zoster virus(VZV).Here,we investigated what kind of cell(s)and which signal molecule(s)are involved in IFN-a production.Using cell isolation and ELISA,we found that plasmacytoid dendritic cells(pDCs)were responsible for IFN-a production during VZV infection.We also found that Toll-like receptor 9(TLR9)was involved in VZV-induced IFN-a production because inhibitory CpG oligodeoxynucleotide inhibited IFN-a production.UV-inactivated VZV-induced IFN-a production was lower than that of active VZV,indicating another TLR9-independent pathway.Further studies demonstrated that double-stranded RNA-dependent protein kinase,but not DNA-dependent protein kinase was involved in VZV-induced IFN-a production.Together,these results suggest that pDCs play an important role in IFN-a production during VZV infection through TLR9-dependent and-independent pathways. | Hong-Ren Yu Hsin-Chun Huang Ho-Chang Kuo Jiunn-Ming Sheen Chia-Yo Ou Te-Yao Hsu Kuender D Yang | 2011 | Cellular & Molecular Immunology2011，8，2： | 7 |
| 18 | TLR2 signaling subpathways regulate TLR9 signaling for the effective induction of IL-12 upon stimulation by heat-killed Brucella abortus显示文摘Brucella 流产胎是在 dentritic 房间(DC ) 和随后的保护的 Th1 有免疫力的回答导致 MyD88 依赖的 IL-12 生产的一个克否定的细胞内部的细菌。以前的研究证明了像使用费的受体(TLR2 ) 2 为肿瘤坏死被要求因素(TNF ) 生产,而 TLR9 为在在到杀死热的 Brucella 流产胎(HKBA ) 的暴露以后的 DC 感应的 IL-12 负责。TLR2 位于房间表面并且被天生的有免疫力的房间为最佳的导致微生物的吞噬作用要求;因此,吞噬作用是为由在 late-endosomal 分隔空间的 TLR9 的细菌的 genomic DNA 识别的不可缺少的初步的步。这里,我们假设了那在通过 DC 的吞噬细胞的函数的间接调整或 cytokine 的直接调整发信号的 HKBA 刺激力量跨 regulate TLR9 以后的被触发 TLR2 的信号基因表示。我们的结果显示那个 HKBA 吞噬作用是 TLR2 依赖的并且为 IL-12p40 的必要的步感应。另外, HKBA 暴露触发了 p38 和细胞外的调整信号的 kinase 1/2 (ERK1/2 ) 的调停 TLR2 的激活。有趣地,尽管 p38 为 HKBA 吞噬作用和 phagosome 成熟被要求, ERK1/2 没影响这些过程,但是否定地调整 IL-12 生产。尽管 p38 禁止者 tempered 对 HKBA 的 TNF 和 IL-12 回答,有一个 ERK1/2 禁止者的预告的处理显著地增加了 IL-12p40 并且在刺激 HKBA 的 DC 废除了 TNF 生产。进一步的实验证明在 TLR2 被触发以后的那调停的 ERK1/2 激活也要求了的发信号的事件导致 HKBA 的地岬激活。而且, Ras-guanine 释放核苷酸的蛋白质(RasGRP1 ) 1 调停了导致 TLR2 的 ERK1/2 激活和 IL-12p40 的抑制生产。一起拿,我们的结果证明调停 HKBA 的被触发 TLR2 激活 p38 和 ERK1/2 发信号 subpathways,它分叉地在几个层次调整 TLR9 激活导致适当保护的 IL-12 回答。 | Chun-Yan Zhang Nan Bai Zhu-Hong Zhang Ning Liang Lan Dong Rong Xiang Cheng-Hu Liu | 2012 | Cellular & Molecular Immunology2012，9，4： | 7 |
| 19 | 苏合香挥发油对脑缺血再灌注诱导神经细胞损伤的影响显示文摘目的探究苏合香挥发油对脑缺血再灌注诱导神经细胞损伤的影响。方法体外培养大鼠皮层神经细胞,采用糖氧剥夺/再复氧(OGD/R)构建脑缺血再灌注损伤模型,以苏合香挥发油处理。细胞计数试剂盒8(CCK-8)和流式细胞术分别检测神经细胞存活和凋亡,试剂盒检测超氧化物歧化酶(SOD)、丙二醛(MDA)水平,蛋白质印迹法(Western Blot)检测caspase-3和Toll样受体9(TLR9)蛋白表达,实时荧光定量PCR(qPCR)检测TLR9 mRNA表达。在神经细胞中转染si-TLR9并进行I/R处理,或转染pcDNA3.1-TLR9并进行苏合香挥发油和缺血/再灌注处理。结果与脑缺血再灌注损伤模型比较,不同浓度苏合香挥发油可提高脑缺血再灌注损伤的神经细胞存活率、SOD活性(P<0.05),降低凋亡率、caspase-3蛋白表达、MDA水平、TLR9 mRNA和蛋白表达(P<0.05),并均呈浓度依赖性。抑制TLR9可明显增加脑缺血再灌注损伤的神经细胞存活率和SOD活性,显著减少凋亡率、caspase-3蛋白表达和MDA水平。过表达TLR9能减弱苏合香挥发油对脑缺血再灌注损伤的神经细胞存活、SOD活性的促进作用,以及对细胞凋亡率、caspase-3蛋白表达、MDA水平的抑制作用。结论苏合香挥发油可通过下调TLR9表达来促进糖氧剥夺/再复氧诱导的神经细胞增殖,并抑制凋亡,减轻氧化应激损伤,从而保护脑缺血再灌注损伤。 | 陈雨 林高城 白亮 | 2020 | 中成药2020，42，12： | 7 |
| 20 | Toll样受体9基因多态性和幽门螺杆菌感染的关系显示文摘目的探讨Toll样受体9(TLR9)基因多态性与幽门螺杆菌感染的关系。方法选取体检者683例的血液样本,采用酶联免疫吸附测定方法(ELISA)将样本分为幽门螺杆菌阴性组(n=305)和幽门螺杆菌阳性组(n=378),采用聚合酶链式反应-限制性片段长度多态性(PCR-RFLP)法对TLR9 rs187084、rs352140、rs164640位点进行基因分型。结果TLR9 rs187084 TC基因型可使幽门螺杆菌感染风险降低(TC vs TT:OR=0.520,95%CI=0.329~0.820);rs164640携带AG+GG基因型者幽门螺杆菌感染风险增加(AG+GG vs AA:OR=1.569,95%CI=1.126~2.187);rs352140与幽门螺杆菌感染没有关联。结论TLR9 rs187084、rs164640可能在幽门螺杆菌的感染中起到了一定的作用。 | 卫星如 马立聪 田旭阳 党彤 高芳 贾彦彬 | 2020 | 安徽医科大学学报2020，55，1： | 6 |
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