高迁移率族蛋白1(high-mobility group box-1,HMGB1)是新发现的一种"晚期炎症介质",而且高表达于多种肿瘤组织,与其相应受体结合参与调节肿瘤细胞的发生、发展。有研究证实HMGB1的拮抗剂能有效抑制肿瘤细胞的增殖,因而HMGB1...高迁移率族蛋白1(high-mobility group box-1,HMGB1)是新发现的一种"晚期炎症介质",而且高表达于多种肿瘤组织,与其相应受体结合参与调节肿瘤细胞的发生、发展。有研究证实HMGB1的拮抗剂能有效抑制肿瘤细胞的增殖,因而HMGB1有望成为抗肿瘤治疗的一种新的靶分子。展开更多
The pro-inflammation factor high-mobility group box protein 1 （HMGB1） has been implicated in the pathogenesis of asthma. In this study, we used a murine model of chronic asthma to evaluate the effects of HMGB 1 on a...The pro-inflammation factor high-mobility group box protein 1 （HMGB1） has been implicated in the pathogenesis of asthma. In this study, we used a murine model of chronic asthma to evaluate the effects of HMGB 1 on airway remodeling. Female BALB/c mice were randomly divided into four groups： control, ovalbumin （OVA） asthmatic, OVA＋ isotype antibody and OVA＋anti-HMGB 1 antibody. Anti-HMGB 1 antibody therapy was started on day 21 and was administered three times per week for 6 weeks before intranasal challenge with OVA. In this mouse model, HMGB1 expression is significantly elevated. The anti-HMGB1 antibody group exhibited decreased levels of immunoglobulin E （IgE） and inflammatory mediators and reduced inflammatory cell accumulation, airway hyperresponsiveness （AHR）, mucus synthesis, smooth muscle thickness and lung collagen content compared with the OVA groups. Treatment with HMGB1 increased proliferation, migration, collagen secretion and a-smooth muscle actin （SMA） expression in MRC-5 ceils. Treatment with the HMGB1/IL-1β complex significantly increased the expression and secretion of transforming growth factor （TGF-βl）, matrix metalloproteinase （MMP）-9 and vascular endothelial growth factor （VEGF）. Altogether, these results suggest that blocking HMGB1 activity may reverse airway remodeling by suppressing airway inflammation and modulating lung fibroblast phenotype and activation.展开更多
为研究人高迁移率族蛋白B1(high-mobility group box-1,HMGB1)酸性尾端对其抗菌活性的影响,提取人外周血单个核细胞总RNA,经RT-PCR扩增得到编码人HMGB1的cDNA及其缺失酸性尾端的突变体cDNA(mcDNA),原核表达载体pQE-80L分别表达重组人HM...为研究人高迁移率族蛋白B1(high-mobility group box-1,HMGB1)酸性尾端对其抗菌活性的影响,提取人外周血单个核细胞总RNA,经RT-PCR扩增得到编码人HMGB1的cDNA及其缺失酸性尾端的突变体cDNA(mcDNA),原核表达载体pQE-80L分别表达重组人HMGB1蛋白(rhHMGB1)及缺失酸性尾端的突变体蛋白(mrhHMGB1),经Ni2+-NTA亲和层析柱纯化两种蛋白.通过试管稀释法、琼脂扩散法两种体外抗菌实验观察,并比较rhHMGB1及mrhHMGB1抗菌活性的差异.实验结果显示,rhHMGB1对大肠杆菌JM109、ATCC25922、DH5α有明确的抗菌活性,其抗菌活性强弱依次为JM109>ATCC25922>DH5α,而mrhHMGB1对大肠杆菌JM109、ATCC25922、DH5α则均无抗菌活性.实验结果表明,人HMGB1的酸性尾端对其抗菌活性的发挥至关重要,此研究为进一步探讨人HMGB1抗菌功能的机制奠定了基础.展开更多
高迁移率族蛋白1(high mobility group box 1,HMGB1)是一种高度保守的DNA结合蛋白,与核小体结构的修复及基因转录调控密切相关。HMGB1由坏死细胞或活化的单核/巨噬细胞被动或主动释放至细胞外,并发挥促炎和修复作用。脓毒症是一种全身...高迁移率族蛋白1(high mobility group box 1,HMGB1)是一种高度保守的DNA结合蛋白,与核小体结构的修复及基因转录调控密切相关。HMGB1由坏死细胞或活化的单核/巨噬细胞被动或主动释放至细胞外,并发挥促炎和修复作用。脓毒症是一种全身炎症反应综合征。发生脓毒症时,血清和组织中HMGB1浓度上升,HMGB1在其发生过程中扮演晚期促炎细胞因子的角色。在脓毒症和内毒素血症动物模型中,靶向给予HMGB1抗体或特异性拮抗剂可以改善预后。本文就HMGB1的结构、在细胞核内发挥的作用、释放过程和其在炎症反应及脓毒症中发挥的作用研究进展作一综述。展开更多
Objective： To detect the expression profiles of micro RNA-218（mi R-218） in human pancreatic cancer tissue（PCT） and cells and their effects on the biological features of human pancreatic cancer cell line PANC-1 an...Objective： To detect the expression profiles of micro RNA-218（mi R-218） in human pancreatic cancer tissue（PCT） and cells and their effects on the biological features of human pancreatic cancer cell line PANC-1 and observe the effect of mi R-218 on the expression of the target gene high mobility group box 1（HMGB1）, with an attempt to provide new treatment methods and strategies for pancreatic cancer.Methods： The expressions of mi R-218 in PCT and normal pancreas tissue as well as in various pancreatic cancer cell lines including As PC-1, Bx PC-3, and PANC-1 were determined with quantitative real-time reverse transcription polymerase chain reaction（q RT-PCR）. The change of mi R-218 expression in PANC-1 cells was detected using qR T-PCT after the transfection of miR-218 mimic for 48 h. Cell Counting Kit-8（CCK-8） was applied for detecting the effect of mi R-218 on the activity of PANC-1 cells. The effects of mi R-218 on the proliferation and apoptosis of PANC-1 cells were analyzed using the flow cytometry. The effect of mi R-218 on the migration of PANC-1 cells was detected using the Trans-well migration assay. The HMGB1 was found to be a target gene of mi R-218 by luciferase reporter assay, and the effect of mi R-218 on the expression of HMGB1 protein in cells were determined using Western blotting.Results： As shown by q RT-PCR, the expressions of mi R-218 in PCT and in pancreatic cancer cell line significantly decreased when compared with the normal pancreatic tissue（NPT）（P〈0.01）. Compared with the control group, the miR-218 expression significantly increased in the PANC-1 group after the transfection of mi R-218 mimic for 48 h（P〈0.01）. Growth curve showed that the cell viability significantly dropped after the overexpression of mi R-218 in the PANC-1 cells for two days（P〈0.05）. Flow cytometry showed that the S-phase fraction significantly dropped after the overexpression of mi R-218（P〈0.01） and the percentage of apoptotic cells significantly increased（P〈0.0展开更多
目的:探讨miR-129-5p通过调控高迁移率族蛋白B1基因(high mobility group box 1,HMGB1)影响乳腺癌MCF-7细胞对紫杉醇(paclitaxel,PTX)的敏感性。方法:采用脂质体转染技术将miR-129-5p mimics、HMGB1小干扰RNA(si-HMGB1)分别转染入MCF-7...目的:探讨miR-129-5p通过调控高迁移率族蛋白B1基因(high mobility group box 1,HMGB1)影响乳腺癌MCF-7细胞对紫杉醇(paclitaxel,PTX)的敏感性。方法:采用脂质体转染技术将miR-129-5p mimics、HMGB1小干扰RNA(si-HMGB1)分别转染入MCF-7细胞,用PTX刺激培养细胞后,用实时荧光定量PCR检测转染后MCF-7细胞miR-129-5p和HMGB1 m RNA的表达,Western blotting检测转染后MCF-7细胞HMGB1蛋白的表达,CCK-8增殖实验检测转染后PTX对MCF-7细胞增殖的影响,流式细胞术检测转染后对PTX诱导MCF-7细胞凋亡的影响。结果:转染miR-129-5p mimics后,MCF-7细胞中miR-129-5p的表达水平明显高于阴性对照组细胞(P<0.01);过表达miR-129-5p后可明显增强PTX抑制MCF-7细胞的增殖和诱导细胞凋亡的能力(均P<0.05),并显著抑制HMGB1 m RNA和蛋白的表达(均P<0.05)。转染si-HMGB1后,显著降低MCF-7细胞HMGB1 m RNA和蛋白的表达(均P<0.05);干扰HMGB1表达进一步促进PTX抑制MCF-7细胞的增殖并诱导细胞凋亡(均P<0.05)。结论:miR-129-5p通过下调HMGB1的表达增强乳腺癌MCF-7细胞对PTX的敏感性。展开更多
观察小剂量LPS（lipopolysaccharide）刺激下非坏死HepG2细胞是否存在HMGB1（high mobility group box—1 protein）移位及释放．以终浓度为100μg／L的LPS作用HepG2和RAW264．7细胞0、4、8、12、16、20、24h．LPS作用16-24h．HepG2和RA...观察小剂量LPS（lipopolysaccharide）刺激下非坏死HepG2细胞是否存在HMGB1（high mobility group box—1 protein）移位及释放．以终浓度为100μg／L的LPS作用HepG2和RAW264．7细胞0、4、8、12、16、20、24h．LPS作用16-24h．HepG2和RAW264．7细胞培养上清中均可以检测到明显的HMGB1，与对照组差别有显著性（P〈0．05）．而MTT法和上清中LDH（lactate dehydrogenase）含量测定显示，LPS处理24h的HepG2存活率仍然非常高．免疫荧光观察到HMGB1的释放伴随着其从细胞核向胞浆的移位．由此可见，经LPS诱导，非坏死状态的HeDG2细胞可发生HMGB1的移位及释放．展开更多
基金This study was supported by the Scientific Research and Technological Development Program Project of Guangxi Province （10124001A-32）, the Young Science Foundation of Guangxi Medical University （GXMUSF201206） and the Innovation Project of Guangxi Graduate Education （YCBZ2013014）.
文摘The pro-inflammation factor high-mobility group box protein 1 （HMGB1） has been implicated in the pathogenesis of asthma. In this study, we used a murine model of chronic asthma to evaluate the effects of HMGB 1 on airway remodeling. Female BALB/c mice were randomly divided into four groups： control, ovalbumin （OVA） asthmatic, OVA＋ isotype antibody and OVA＋anti-HMGB 1 antibody. Anti-HMGB 1 antibody therapy was started on day 21 and was administered three times per week for 6 weeks before intranasal challenge with OVA. In this mouse model, HMGB1 expression is significantly elevated. The anti-HMGB1 antibody group exhibited decreased levels of immunoglobulin E （IgE） and inflammatory mediators and reduced inflammatory cell accumulation, airway hyperresponsiveness （AHR）, mucus synthesis, smooth muscle thickness and lung collagen content compared with the OVA groups. Treatment with HMGB1 increased proliferation, migration, collagen secretion and a-smooth muscle actin （SMA） expression in MRC-5 ceils. Treatment with the HMGB1/IL-1β complex significantly increased the expression and secretion of transforming growth factor （TGF-βl）, matrix metalloproteinase （MMP）-9 and vascular endothelial growth factor （VEGF）. Altogether, these results suggest that blocking HMGB1 activity may reverse airway remodeling by suppressing airway inflammation and modulating lung fibroblast phenotype and activation.
文摘为研究人高迁移率族蛋白B1(high-mobility group box-1,HMGB1)酸性尾端对其抗菌活性的影响,提取人外周血单个核细胞总RNA,经RT-PCR扩增得到编码人HMGB1的cDNA及其缺失酸性尾端的突变体cDNA(mcDNA),原核表达载体pQE-80L分别表达重组人HMGB1蛋白(rhHMGB1)及缺失酸性尾端的突变体蛋白(mrhHMGB1),经Ni2+-NTA亲和层析柱纯化两种蛋白.通过试管稀释法、琼脂扩散法两种体外抗菌实验观察,并比较rhHMGB1及mrhHMGB1抗菌活性的差异.实验结果显示,rhHMGB1对大肠杆菌JM109、ATCC25922、DH5α有明确的抗菌活性,其抗菌活性强弱依次为JM109>ATCC25922>DH5α,而mrhHMGB1对大肠杆菌JM109、ATCC25922、DH5α则均无抗菌活性.实验结果表明,人HMGB1的酸性尾端对其抗菌活性的发挥至关重要,此研究为进一步探讨人HMGB1抗菌功能的机制奠定了基础.
文摘高迁移率族蛋白1(high mobility group box 1,HMGB1)是一种高度保守的DNA结合蛋白,与核小体结构的修复及基因转录调控密切相关。HMGB1由坏死细胞或活化的单核/巨噬细胞被动或主动释放至细胞外,并发挥促炎和修复作用。脓毒症是一种全身炎症反应综合征。发生脓毒症时,血清和组织中HMGB1浓度上升,HMGB1在其发生过程中扮演晚期促炎细胞因子的角色。在脓毒症和内毒素血症动物模型中,靶向给予HMGB1抗体或特异性拮抗剂可以改善预后。本文就HMGB1的结构、在细胞核内发挥的作用、释放过程和其在炎症反应及脓毒症中发挥的作用研究进展作一综述。
基金supported by grants:Liaoning Provincial Department of education science research project(L2014299)Liaoning province science and technology plan project(2011404013-4)The Shenyang Municipal Science and technology project(F12-277-1-73)
文摘Objective： To detect the expression profiles of micro RNA-218（mi R-218） in human pancreatic cancer tissue（PCT） and cells and their effects on the biological features of human pancreatic cancer cell line PANC-1 and observe the effect of mi R-218 on the expression of the target gene high mobility group box 1（HMGB1）, with an attempt to provide new treatment methods and strategies for pancreatic cancer.Methods： The expressions of mi R-218 in PCT and normal pancreas tissue as well as in various pancreatic cancer cell lines including As PC-1, Bx PC-3, and PANC-1 were determined with quantitative real-time reverse transcription polymerase chain reaction（q RT-PCR）. The change of mi R-218 expression in PANC-1 cells was detected using qR T-PCT after the transfection of miR-218 mimic for 48 h. Cell Counting Kit-8（CCK-8） was applied for detecting the effect of mi R-218 on the activity of PANC-1 cells. The effects of mi R-218 on the proliferation and apoptosis of PANC-1 cells were analyzed using the flow cytometry. The effect of mi R-218 on the migration of PANC-1 cells was detected using the Trans-well migration assay. The HMGB1 was found to be a target gene of mi R-218 by luciferase reporter assay, and the effect of mi R-218 on the expression of HMGB1 protein in cells were determined using Western blotting.Results： As shown by q RT-PCR, the expressions of mi R-218 in PCT and in pancreatic cancer cell line significantly decreased when compared with the normal pancreatic tissue（NPT）（P〈0.01）. Compared with the control group, the miR-218 expression significantly increased in the PANC-1 group after the transfection of mi R-218 mimic for 48 h（P〈0.01）. Growth curve showed that the cell viability significantly dropped after the overexpression of mi R-218 in the PANC-1 cells for two days（P〈0.05）. Flow cytometry showed that the S-phase fraction significantly dropped after the overexpression of mi R-218（P〈0.01） and the percentage of apoptotic cells significantly increased（P〈0.0
文摘目的:探讨miR-129-5p通过调控高迁移率族蛋白B1基因(high mobility group box 1,HMGB1)影响乳腺癌MCF-7细胞对紫杉醇(paclitaxel,PTX)的敏感性。方法:采用脂质体转染技术将miR-129-5p mimics、HMGB1小干扰RNA(si-HMGB1)分别转染入MCF-7细胞,用PTX刺激培养细胞后,用实时荧光定量PCR检测转染后MCF-7细胞miR-129-5p和HMGB1 m RNA的表达,Western blotting检测转染后MCF-7细胞HMGB1蛋白的表达,CCK-8增殖实验检测转染后PTX对MCF-7细胞增殖的影响,流式细胞术检测转染后对PTX诱导MCF-7细胞凋亡的影响。结果:转染miR-129-5p mimics后,MCF-7细胞中miR-129-5p的表达水平明显高于阴性对照组细胞(P<0.01);过表达miR-129-5p后可明显增强PTX抑制MCF-7细胞的增殖和诱导细胞凋亡的能力(均P<0.05),并显著抑制HMGB1 m RNA和蛋白的表达(均P<0.05)。转染si-HMGB1后,显著降低MCF-7细胞HMGB1 m RNA和蛋白的表达(均P<0.05);干扰HMGB1表达进一步促进PTX抑制MCF-7细胞的增殖并诱导细胞凋亡(均P<0.05)。结论:miR-129-5p通过下调HMGB1的表达增强乳腺癌MCF-7细胞对PTX的敏感性。
