Effect of Nuclear Factor-κB on Airway Remodeling in Asthmatic Rats

Summary In order to investigate the effect of nuclear factor-κB (NF-κB) on airway remodeling in asthmatic rats. 18 Wistar rats were divided into three groups: asthmatic group: pyrrolidine dithiocarbamate (PDTC) group, in which rats were injected intraperitoneally with NF-κB specific inhibitor PDTC (100 mg/kg) before ovalbumin (OVA) challenge; control group. The NF-κB activity and the expression of inhibitory protein κBα (I-κBα) in airway were detected by electrophoretic mobility shift assay (EMSA). Western blot and immunohistochemistry respectively. The infiltration of inflammatory cells, the number of Goblet cells, the area of collagen and smooth muscle in airway were measured by means of image analysis system. The results showed that with the up-regulation of airway NF-κB activity in asthmatic group, the number of goblet cells (3.08±0.86/100 μm basement membrane (BM)), the area of collagen (24.71±4.24 μm²/μm BM) and smooth muscle (13.81±2.11 μm²/μmBM) in airway were significantly increased (P<0.05) as compared with control group (0.14±0.05/100μmBM. 14.31±3.16 μm²/μm BM and 7.67±2.35 μm²/μm BM respectively) and PDTC group (0.33±0.14/100 μmBM, 18.16±2.85 μm²/μm BM and 8.95±2.16 μm²/μm BM respectively). However, there was no significant difference between PDTC group and control group (P>0.05). It was concluded that the activity of NF-κB is increased in airway of asthmatic rats. Inhibition of NF-κB, activation can attenuate constructional changes in asthma airway, suggesting NF-κB may contribute to asthmatic airway remodeling. XU Shuyun, female, born in 1970, M. D. Ph. D. This project was supported by a grant from Foundation for University Key Teacher by the Ministry of Education (2000 year).     

Effects of Triptolide on the Expression and Activity of NF-κB in Synovium of Collagen-induced Arthritis Rats

Summary： The expression and activity of NF-kB in the synovium of collagen-induced arthritis （CIA） rats was detected in order to investigate the possible therapeutic effects of triptolide on rheumatoid arthritis （RA）. The experimental Wistar rat model of CIA was set up by intradermal injection of emulsion of bovine collagen 11 and the successful rate of setting-up models was evaluated by arthritis index （AI）. Rats were grouped randomly into three groups： normal, model and treatment group. The expression of TNF-α and IL-6 in synovial fluid was detected by ELISA, and the expression and activity of NF kB in synovium by immunohistochemistry method and by electrophoretic mobility shift assay （EMSA） respectively. As compared with normal group, the expression of TNF a and IL-6 in synovia （P〈0. 05）, and the expression and activity of NF-kB （P〈0.05） in synovium were increased in model group. There was statistical difference in above-mentioned indexes between model group and treatment group. Triptolide may play a protective role in IRA via downregulating the expression and activity of NF-kB in synovium.     

Expression of Nuclear Factor-κB in Mouse Uterus during Peri-implantation

To investigate the expression of the subunit p65 of NF-κB and inhibitor kappa B alpha (IκBα) in mouse uterus during peri-implantation, thereby investigating whether transient activation of nuclear factor-κB (NF-κB) takes place during embryo implantation in mice. Immunohistochemical technique was used to examine the expression and localization of p65 in endometrium or deciduas, and Western blot analysis was employed to detect the levels of IκBα protein in mouse endometrium or deciduas. P65 protein was detected in stromal cells, epithelial cells of endometrium as well as in myometrium. Staining was predominately seen in the cytoplasm of the cells. Staining intensity for p65 was stronger in the epithelial compartment than the stromal compartment and myometrium. Staining intensity increased slightly during pregnancy, and it reached a high level on pregnancy day 5 and day 8. In contrast to p65, the level of IκBα protein was lowest on pregnancy day 5 in all groups. Our results suggested that NF-κB may regulate embryo implantation by its transient activation in mice.     

EFFECT OF OXIDIZED-LDL ON NF-κB NUCLEAR TRANSLOCATION IN AORTIC SMOOTH MUSCLE CELLS ORIGINATED FROM RATS OF DIFFERENT AGES

Objective To investigate the molecular mechanism of atherosclerosis that related to age. Methods Immunohistochemistry staining and Western blot were adopted to determine the nuclear translocation of nuclear factor-kappa B (NF-κB) and expression of platelet-derived growth factor B (PDGF-B) in smooth muscle cells(SMCs) co-cultured with low density lipoprotein (LDL), oxidized LDL (ox-LDL), and ox-LDL high density lipoprotein(HDL) originated fi‘om rats of 2 and l0 months old respectively. Fat stain was used to identify the lipid intake in SMCs. Results The optimal stimulation time ofox-LDL to SMCs was 12 hours. NF-KB intensity increased in most nuclei of SMCs that originated fi‘om rats of either 2 or l0 months old co-cultured with ox-LDL. The intensity of NF-KB and the amount of intracellular lipid taken in SMCs were more obvious in cells fi‘om 10-month-old rats than fi‘om the younger ones.Change of PDGF-B expression in SMCs was not remarkable in each group of rats. Conclusions The 10-month-old rats are more susceptive to ox-LDL than 2-month-old rats in activating nuclear translocation of NF-KB. Maybe this is one of the important reasons contributing to the difference between the older and younger rats on the initiation and development of atherosclerosis lesion. Expression of PDGF-B is not associated with the activity of nuclear translocation of NF-κB.     

The Role of IκBα in TNF-α-induced Apoptosis in Hepatic Stellate Cell Line HSC-T6

To investigate the role of NF-κB in TNF-α induced apoptosis in HSC-T6, a mutant IκBα was transfected into HSC-T6 cells by lipofectin transfection technique and its transient effect was examined 48 h after the transfection. The activation of NF-κB was detected by immune fluorescence cytochemistry and Western blotting with anti-p65 antibody. The apoptosis and the rate of inhibition by TNF-α in both transfected and untransfected HSC-T6 cells were measured respectively by FAC-Scan side scatter analysis and MTF methods. Our results showed that TNF-α could activate NF-κB in untransfected cells but not in transfected HSC-T6 cells. The percentage of apoptosis in transfected cells were significantly higher than that in the untransfected ones （P〈0.01） and it was also true of the inhibition rate （P〈0.01）. It is concluded that the resistance of HSC-T6 towards apoptosis induced by TNF-α can be mediated by NF-κB activation. The inhibition of NF-κB activation by mutant IκBα can attenuate the resistance of HSC-T6 cells and increase its sensitivity to TNF-α.     

NF-κB信号转导通路与胰岛素抵抗

核因子-κB(NF-κB)信号转导通路包括NF-κB、NF-κB抑制蛋白(IκB)和IκB激酶(IKK).其中,NF-κB是一种重要的核转录因子,参与炎症反应、免疫反应、细胞凋亡及物质代谢等多种生物进程.IKK具有丝氨酸/苏氨酸激酶活性,能使多种蛋白的丝氨酸/苏氨酸残基磷酸化.NF-κB信号转导通路的活化与胰岛素抵抗的发生密切相关.文章就NF-κB在胰岛素抵抗发生中作用作一综述.     

NF-κB信号转导通路与胰岛素抵抗

核因子-κB（NF—κB）信号转导通路包括NF—κB、NF—κB抑制蛋白（IκB）和IκB激酶（IKK）。其中,NF—κB是一种重要的核转录因子,参与炎症反应、免疫反应、细胞凋亡及物质代谢等多种生物进程。IKK具有丝氨酸／苏氨酸激酶活性,能使多种蛋白的丝氨酸／苏氨酸残基磷酸化。NF—κB信号转导通路的活化与胰岛素抵抗的发生密切相关。文章就NF—κB在胰岛素抵抗发生中作用作一综述。     

核因子-κB与肺纤维化

核因子-κB（Nnuculear factor-κB，NF-κB）系1986年从B细胞核抽提物中找到的转录因子，能与免疫球蛋白κ轻链基因增强子B序列GGGACTTTCC特异性结合，并能促进κ轻链基因表达。现已证明NF-κB是一种具有转录激活功能的蛋白质，它能与多种基因启动子或增强子部位κB位点发生特异性结合并促进其转录，是细胞中一个重要的二聚化合物转录因子，能结合DNA的蛋白因子家族。参与许多前炎症介质分子转录水平的调控，包括细胞因子、粘附分子、趋化因子、炎症因子、氧化应激相关酶等，从而促进器官的纤维化。     

核因子-κB对感染性休克大鼠肾功能的影响

目的观察核因子-κB(NF-κB)对感染性休克大鼠肾功能的影响,探讨感染性休克时肾功能降低的机制。方法将20只大鼠随机分为2组,每组10只。实验组采用盲肠结扎穿孔术(CLP)制作感染性休克模型,对照组不进行CLP术,其余操作同实验组。各组均测定肾脏组织NF-κB蛋白表达及肾功能情况。结果实验组CLP术后12 h肾组织NF-κB蛋白表达升高,与对照组比较有显著差异(P<0.01);实验组CLP术后12 h血清尿素氮及肌酐增加,与对照组比较有显著差异(P<0.01)。结论CLP所致大鼠感染性休克过程中,肾组织NF-κB蛋白表达升高,可能是导致肾功能减退的重要因素。     

Expression of NF-κB in hRPE Cells Stimulated by PDTC and IL-1β

The constitutive expression of nuclear-factor-κB (NF-κB) in human pigment epithelial (hRPE) cells cultivated in vitro and the possible changes when incubated with PDTC and IL-I were investigated. The synchronized hRPE cells in vitro were divided into two groups. In nonPDTC group, hRPE cells were exposed respectively to IL-1β and NS (for detecting the constitutive expressions of NF-κB in hRPE cells) ; In PDTC group, PDTC-pretreated hRPE cells were exposed respectively to IL-1β?Aand NS. (for detecting the constitutive expression of NF-κB in PDTC-pretreated hRPE cells). The expression of NF-κB in hRPE cells in two groups was detected by immunofluorescence stain and flow cytometry. The results showed that the constitutive expression of NF-κB in hRPE cells in vitro was 8.05 %, and increased to 30.26 % by IL-1β. After PDTC pretreatment, the constitutive expression of NF-κB in hRPE cells was decreased to 3.74%, and 3.66 % by IL-l,respectively. It was concluded that the expressions of NF-κB in hRPE cells could be increased significantly by IL-1βand depressed effectively by PDTC. Also, PDTC could significantly inhibit the activation of NF-κB induced by IL-1β.     

核因子-κB与败血症

核因子-κB(NF-κB)是近期发现并研究较多的一种重要的转录因子,能与免疫、细胞生长和炎症反应相关的许多细胞因子、粘附分子基因的启动子/增强子部位的κB位点发生特异性结合,启动和调节这些基因的转录,在这些因子基因的转录调控中发挥一定作用,在机体的免疫应答、炎症反应及细胞的生长调控等方面发挥重要作用,成为相关疾病治疗的新靶点,越来越受人们的关注.     

感染性休克大鼠心功能改变及心肌细胞中核因子-κB的表达

目的观察感染性休克大鼠心功能的改变及心肌细胞中核因子-κB(NF-κB)的表达。方法将20只大鼠随机分为2组,每组10只。实验组采用盲肠结扎穿孔术(CLP)制作感染性休克模型,对照组不进行CLP术,其余操作同实验组。2组均于12 h后测定心肌组织NF-κB蛋白表达及心功能情况。结果实验组心肌组织内NF-κB阳性表达明显高于对照组,差别有统计学意义(P<0.01);实验组大鼠左室内压上升下降最大速率、左心室收缩末期压、心率、收缩压及舒张压明显低于对照组,而左心室舒张末期压明显高于对照组,差别均有统计学意义(P<0.01)。结论CLP所致感染性休克大鼠心肌细胞中NF-κB蛋白表达升高可能与大鼠心功能减退有关。     

NF-κB在机械通气和内毒素肺损伤中的作用机制

目的探讨幼兔机械通气、内毒素及机械通气复合内毒素肺损伤时,肺组织核因子-κB(NF-κB)活化及其对TNF-α和IL-8表达的影响.方法60只普通级幼兔随机等分为对照组(NMV)、大潮气量组(LVMV)、内毒素组(ENMV)和复合损伤组(EMV)(n=15),检测各时相肺组织NF-κB活性、IκBα含量、TNF-α和IL-8的基因表达和蛋白含量变化,并观察肺组织病理改变.结果NF-κB活性在NMV较底,ENMV致伤后2 h NF-κB活性达最高,而LVMV通气4 h NF-κB活性达高峰;EMV伤后各时相点NF-κB活性强度显著高于其它两组(P＜0.01).IκBα含量在NMV较高,ENMV致伤后4 hIκBα含量降至最低;出现显著下降的时间早于LVMV;EMV在通气后2、4、6 h的IκBα含量降低程度显著大于其它两组(P＜0.01).TNF-α、IL-8 mRNA和蛋白含量在NMV较低,在ENMV和EMV肺组织伤后TNF-α、IL-8 mRNA和蛋白含量峰值早于LVMV,EMV伤后2、4、6 h TNF-αmRNA表达和蛋白含量显著高于其它两组(P＜0.05,P＜0.01).结论机械通气和内毒素可能通过不同的途径使NF-κB活化,启动致炎细胞因子的转录,导致肺损伤.机械通气和内毒素先后作用于机体对NF-κB的活化可能有相互反应后效应的加强,加重肺损伤.     

NF-κB在机械通气和内毒素肺损伤中的作用机制

目的探讨幼兔机械通气、内毒素及机械通气复合内毒素肺损伤时,肺组织核因子-κB(NF-κB)活化及其对TNF-α和IL-8表达的影响.方法60只普通级幼兔随机等分为对照组(NMV)、大潮气量组(LVMV)、内毒素组(ENMV)和复合损伤组(EMV)(n=15),检测各时相肺组织NF-κB活性、IκBα含量、TNF-α和IL-8的基因表达和蛋白含量变化,并观察肺组织病理改变.结果NF-κB活性在NMV较底,ENMV致伤后2 h NF-κB活性达最高,而LVMV通气4 h NF-κB活性达高峰;EMV伤后各时相点NF-κB活性强度显著高于其它两组(P＜0.01).IκBα含量在NMV较高,ENMV致伤后4 hIκBα含量降至最低;出现显著下降的时间早于LVMV;EMV在通气后2、4、6 h的IκBα含量降低程度显著大于其它两组(P＜0.01).TNF-α、IL-8 mRNA和蛋白含量在NMV较低,在ENMV和EMV肺组织伤后TNF-α、IL-8 mRNA和蛋白含量峰值早于LVMV,EMV伤后2、4、6 h TNF-αmRNA表达和蛋白含量显著高于其它两组(P＜0.05,P＜0.01).结论机械通气和内毒素可能通过不同的途径使NF-κB活化,启动致炎细胞因子的转录,导致肺损伤.机械通气和内毒素先后作用于机体对NF-κB的活化可能有相互反应后效应的加强,加重肺损伤.     

NF-κB和TNF-α在烟曲霉菌感染小鼠肺组织中的表达

目的探讨核因子-κB(NF-κB)和肿瘤坏死因子-α(TNF-α)在小鼠抗烟曲霉菌早期感染中的作用。方法将小鼠分4组:正常组、免疫抑制组、正常+烟曲霉菌接种组和IPA模型组。小鼠鼻吸入烟曲霉菌48 h处死,取肺组织用western blot法检测胞核NF-κB p65蛋白和细胞中TNF-α的表达。结果正     

核因子-κB在皮肤病中的研究进展

核因子-κB是一种具有多项转录调节作用的蛋白质,通过调节免疫和炎症相关因子及炎症递质的表达,在炎症和免疫反应中起枢纽作用,此外在细胞增殖和凋亡相关基因的调控中也起关键作用。多种皮肤病,如银屑病、结缔组织病、特应性皮炎、皮肤肿瘤等与核因子-κB途径的失调有关,本文就核因子-κB的组成、功能及在皮肤病发病机制中的研究进展作一综述。     

核因子-κB活化对大鼠烧伤早期肺组织表达促炎细胞因子的作用

目的 探讨核因子-κB(NF-κB)在大鼠烧伤早期肺组织表达促炎细胞因子中的作用.方法 采用Wistar大鼠Ⅲ度35%TBSA烧伤模型.实验分正常对照组、烧伤组、烧伤后吡咯烷二硫代氨基甲酸盐干预组(PDTC组).大鼠烧伤后1、3、6、12、24 h凝胶电泳迁移率分析法检测肺组织NF-κB活性;逆转录-聚合酶链式反应检测TNFo、IL-8 mRNA的表达.结果 大鼠烧伤后肺组织NF-κB活性在伤后1 h内即迅速增高,并持续增高到伤后24 h.伤后肺组织TNFα、IL-8mRNA表达逐渐增多,6 h达高峰.PDTC组NF-κB活性降低,肺组织TNFα和IL-8 mRNA表达均较对照组明显减少.结论 严重烧伤可活化肺组织NF-κB,从而介导对细胞因子的合成和释放.提示NF-κB活化在烧伤后脏器组织细胞表达释放细胞因子过程中起重要作用.