核转录因子κB在神经干细胞发育中的作用

目的:核转录因子κB是一种可激活的转录因子,存在于脑内神经元、神经胶质和神经干细胞中,参与体内炎症和免疫反应、发育、凋亡和抗凋亡等众多生物过程。本文就核转录因子κB在神经干细胞增殖、迁移和分化中的作用进行综述。资料来源:应用计算机检索PUBMED1987-01/2006-09期间的相关文章,检索词为“Neural stem cell,Proliferation,Migration,Differentiation/stem cell,Differentiation/NF-κB”,并限定文章语言种类为English。资料选择:对资料进行初审,并查看每篇文献后的引文。纳入标准:文章所述内容应与核转录因子κB在神经干细胞增殖、迁移和分化中的作用相关。排除标准:重复研究或Meta分析类文章。资料提炼:共收集到61篇相关文献,32篇文献符合纳入标准,排除的29篇文献为内容陈旧或重复。符合纳入标准的32篇文献中,4篇涉及成体神经干细胞,3篇涉及转录因子κB/Rel家族和I-κB蛋白,11篇涉及核转录因子κB与神经干细胞增殖,8篇涉及核转录因子κB与神经干细胞的迁移,6篇涉及核转录因子κB与神经干细胞分化。资料综合:神经干细胞是一类具有自我更新、高度增殖、定向迁移和多向分化潜能的细胞群体,可存在于成熟脑的特定区域。神经干细胞的发育经历着分裂、迁移和分化成熟的过程。核转录因子κB是一种具有多向转录调节作用的蛋白质,可与特定DNA片段结合,调节相关基因的转录。核转录因子κB参与了促红细胞生成素、缺氧及脑损伤等引起的神经干细胞增殖,在使用其抑制剂如β-淀粉样蛋白、一氧化氮等后,神经干细胞增殖减少。在神经干细胞迁移方面,核转录因子κB通过诱导巨噬细胞化学诱导蛋白1、干细胞因子、基质细胞衍生因子等的表达而达到促进神经干细胞迁移的作用。神经干细胞向星型胶质细胞、神经元、少突胶质细胞和神经胶质谱系分化是由特定的信号级联决定的,细胞因子白细胞介素6家族通过激活核转录因子κB而促进神经干细胞向星形胶质细胞的分化,成神经瘤细胞的分化过程必需有核转录因子κB的参与。结论:大量证据表明在神经干细胞复杂的转录调节机制中,核转录因子κB发挥着重要的作用。     

NF-κB在肝细胞及肝脏疾病中作用的研究进展

核因子-κB(NF-κB)是近年来研究极为广泛的转录调控因子,具有多种转录调节活性。参与细胞因子、活化因子、生长因子和粘附分子及某些急性期反应蛋白转录活性的调控,在正常及疾病状态下、在肿瘤的发生和发展过程中有重要作用。NF-κB在肝细胞、肝癌细胞都有表达,在肝移植、肝缺血再灌注损伤等病理生理过程中均发挥重要作用。     

NF-κB在肝细胞及肝脏疾病中作用的研究进展

核因子-κB（NF-κB）是近年来研究极为广泛的转录调控因子，具有多种转录调节活性。参与细胞因子、活化因子、生长因子和粘附分子及某些急性期反应蛋白转录活性的调控，在正常及疾病状态下、在肿瘤的发生和发展过程中有重要作用。NF-κB在肝细胞、肝癌细胞都有表达，在肝移植、肝缺血再灌注损伤等病理生理过程中均发挥重要作用。     

核因子-κB与肝脏疾病研究进展

核因子-κB(NF-κB)是近年来研究最为广泛的转录调控因子,具有多种转录调控活性,决定细胞因子、生长因子、细胞黏附分子、一氧化氮合酶(NOS)、环氧化酶2(COX-2)及某些急性期反应蛋白转录活性的调控。在正常和疾病状态下均有广泛表达。存在于细胞质中的NF-κB与抑制蛋白I-κB形成无生     

神经系统功能损伤与核转录因子κB的激活

目的:核转录因子κB活化后促进许多靶基因表达,参与免疫调节、细胞凋亡和细胞发育。核转录因子κB可在多种神经系统疾病中被激活,探讨其在疾病发生发展中所起的作用。资料来源:应用计算机检索Medline1994-01/2004-12与核转录因子κB和神经系统疾病相关的文章,检索词“NF-kappaB,braininjury,cytokine”,并限定文章语言种类为English。资料选择:对资料进行初审,选取符合文章主题的随机对照实验,不排除是否为盲法研究,无论临床和基础研究全部纳入,排除综述。资料提炼:共收集到29篇关于“核转录因子κB与神经系统疾病”的临床和基础研究,23篇符合纳入标准,排除的6篇文章系重复实验。资料综合:23篇文章从基因和分子水平对核转录因子κB的生物学特点和在神经系统疾病中的作用机制进行了阐述。核转录因子κB可在多种神经系统损伤中被激活,如脑损伤、脑梗死、脑炎、阿尔茨海默病等。它对于神经疾病的作用具有双重性,既可引起神经细胞凋亡,又可通过诱导抗凋亡蛋白表达而阻止细胞凋亡,在阿尔茨海默病中可能既参与毒性作用,又参与神经细胞保护机制。结论:核转录因子κB与神经系统疾病关系紧密,通过对其机制的深入研究,可望为脑缺血、脑炎、神经变性等疾病的治疗开辟新的途径。     

核因子Κb与Th细胞分化

核因子κB是一种广泛存在于体内多种细胞的转录因子,由一个复杂的体系组成,目前已发现它调节着100多种靶基因的表达。能与调控免疫应答、炎症反应、细胞分化和生长、细胞粘附和细胞凋亡所必需的许多细胞因子,粘附因子等基因启动子或增强子部位的κB位点发生特异性结合,启动和调节这些基因的转录,在机体的免疫应答、炎症反应和细胞的生长生育等方面发挥重要作用。本文复习相关文献,对NF-κB及其对Th细胞分化的调节作一综述。1核因子-κB的生物学特性1.1核因子-κB的组成核因子-κB是一种多向性核转录因子,是Sen[1]等1986年首次在成熟B细…     

核转录因子-κB在急性肾损伤细胞凋亡中的作用

急性肾损伤是临床常见的危重症,病死率高,缺乏有效的防治措施.研究发现,细胞凋亡在急性肾损伤的发生机制中起着重要作用.核转录因子-κB (NF-κB)是具有多向转录调节作用的核蛋白因子,与细胞凋亡关系密切,参与多种凋亡相关基因的转录调控,具有抑制和促进细胞凋亡的双向作用.本文就NF-κB信号传导在急性肾损伤细胞凋亡中的作用作一综述.     

神经系统功能损伤与核转录因子κB的激活

目的：核转录因子κB活化后促进许多靶基因表达，参与免疫调节、细胞凋亡和细胞发育。核转录因子κB可在多种神经系统疾病中被激活，探讨其在疾病发生发展中所起的作用。资料来源：应用计算机检索Medline1994-01／2004-12与核转录因子κB和神经系统疾病相关的文章，检索词“NF-kappaB，brain injury，cytokine”，并限定文章语言种类为English。资料选择：对资料进行初审，选取符合文章主题的随机对照实验，不排除是否为盲法研究，无论临床和基础研究全部纳入，排除综述。资料提炼：共收集到29篇关于“核转录因子κB与神经系统疾病”的临床和基础研究，23篇符合纳入标准，排除的6篇文章系重复实验。资料综合：23篇文章从基因和分子水平对核转录因子κB的生物学特点和在神经系统疾病中的作用机制进行了阐述。核转录因子κB可在多种神经系统损伤中被激活，如脑损伤、脑梗死、脑炎、阿尔茨海默病等。它对于神经疾病的作用具有双重性，既可引起神经细胞凋亡，又可通过诱导抗凋亡蛋白表达而阻止细胞凋亡，在阿尔茨海默病中可能既参与毒性作用，又参与神经细胞保护机制。结论：核转录因子κB与神经系统疾病关系紧密，通过对其机制的深入研究，可望为脑缺血、脑炎、神经变性等疾病的治疗开辟新的途径。     

NF-κB在泌尿系肿瘤中的研究进展

核因子κB(nuclear factor-kappa B,NF-κB)又称核转录因子,具有和某些基因上启动子区的固定核苷酸序列结合而启动基因转录的功能.在非激活条件下,NF-κB在大多数细胞类型的细胞浆内与其抑制蛋白IκB家族紧密结合而呈无活性状态.NF-κB在激活后,从细胞质进入细胞核参与调控多种基因的转录.大量研究表明,它可以被多种刺激剂,如TNF-α、IL-1、蛋白激酶C激活剂、脂多糖(LPS)等激活[1-2].NF-κB广泛存在于各种细胞中,通过调控细胞激酶、趋化因子、生长因子、细胞黏附因子及早期反应的蛋白质分子基因的转录而参与炎症和免疫反应、细胞凋亡、细胞增殖分化和迁移等病理生理过程[3].其持续活化可作为多种实体肿瘤的标志,现就其与泌尿系肿瘤关系的研究进展作一综述.     

The inhibition of PI3K and NFκB promoted curcumin-induced cell cycle arrest at G2/M via altering polyamine metabolism in Bcl-2 overexpressing MCF-7 breast cancer cells

Bcl-2 protein has been contributed with number of genes which are involved in oncogenesis. Among the many targets of Bcl-2, NFκB have potential role in induction of cell cycle arrest. Curcumin has potential therapeutic effects against breast cancer through multiple signaling pathways. In this study, we investigated the role of curcumin in induction of cell cycle arrest via regulating of NFκB and polyamine biosynthesis in wt and Bcl-2+ MCF-7 cells. To examine the effect of curcumin on cell cycle regulatory proteins, PI3K/Akt, NFκB pathways and polyamine catabolism, we performed immunoblotting assay. In addition, cell cycle analysis was performed by flow cytometry. The results indicated that curcumin induced cell cycle arrest at G2/M phase by downregulation of cyclin B1 and Cdc2 and inhibited colony formation in MCF-7 wt cells. However, Bcl-2 overexpression prevented the inhibition of cell cycle associated proteins after curcumin treatment. The combination of LY294002, PI3K inhibitor, and curcumin induced cell cycle arrest by decreasing CDK4, CDK2 and cyclin E2 in Bcl-2+ MCF-7 cells. Moreover, LY294002 further inhibited the phosphorylation of Akt in Bcl-2+ MCF-7 cells. Curcumin could suppress the nuclear transport of NFκB through decreasing the interaction of P-IκB-NFκB. The combination of wedelolactone, NFκB inhibitor, and curcumin acted different on SSAT expression in wt MCF-7 and Bcl-2+ MCF-7 cells. NFκB inhibition increased the SSAT after curcumin treatment in Bcl-2 overexpressed MCF-7 cells. Inhibition of NFκB activity as well as suppression of ROS generation with NAC resulted in the partial relief of cells from G2/M checkpoint after curcumin treatment in wt MCF-7 cells. In conclusion, the potential role of curcumin in induction of cell cycle arrest is related with NFκB-regulated polyamine biosynthesis.     

Curcumin enhances the effect of cisplatin in suppression of head and neck squamous cell carcinoma via inhibition of IKKβ protein of the NFκB pathway

Previous experiments have shown that curcumin or cisplatin treatment suppresses growth of head and neck squamous cell carcinoma (HNSCC). To study the potential cooperative effect of both agents, two HNSCC cell lines were treated with curcumin or cisplatin alone or in combination. In vivo studies consisted of intravenous tail vein injection of liposomal curcumin, with intraperitoneal cisplatin, into nude mice growing xenograft HNSCC tumors. Introduction of curcumin and suboptimal concentrations of cisplatin showed a significant suppressive effect compared with treatment with either agent alone. Reduced expression of cyclin D1, IκBα, phospho-IκBα, and IKKβ occurred in cisplatin- and curcumin-treated cell lines. Confocal microscopy showed expression of IKKβ in the nucleus of the cell lines. Chromatin immunoprecipitation assay on DNA isolated from IKKβ immunoprecipitated samples showed PCR amplification of interleukin-8 promoter sequences, a binding site of NFκB, indicating an interaction between IKKβ and NFκB. Curcumin inhibited IKKβ in the cytoplasm and nucleus, leading to reduced NFκB activity, with no effect on phospho-AKT. In vivo studies showed significant growth inhibition of xenograft tumors treated with a combination of liposomal curcumin and cisplatin. The suppressive effect of curcumin was mediated through inhibition of cytoplasmic and nuclear IKKβ, resulting in inhibition of NFκB activity. Cisplatin treatment led to cellular senescence, indicating an effect mediated by p53 activation. The mechanisms of the two agents through different growth signaling pathways suggest potential for the clinical use of subtherapeutic doses of cisplatin in combination with curcumin, which will allow effective suppression of tumor growth while minimizing the toxic side effects of cisplatin.     

核因子κB的反义寡核苷酸对肿瘤坏死因子α诱导的血管细胞黏附分子-1表达的影响

目的：探讨人脐静脉内皮细胞（HUVECs）ECV304细胞株中，核因子κB（NF—κB）的反义寡核苷酸（AODNs）对肿瘤坏死因子α（TNF—α）诱导血管细胞黏附分子（VCAM-1）表达的影响。方法：将培养的人脐静脉内皮细胞株ECV304分为3组，其中2组用脂质体介导法转染寡核苷酸（ODNs）分别转染AODNs、正义寡核苷酸（SODNs）：另1组（阳性对照组）不转染ODNs。流式细胞仪荧光活细胞计数检测转染效率及NF-κB的表达情况，逆转录-聚合酶链反应、流式细胞仪检测及免疫组织化学染色测定AODNs对TNF—α诱导的VCAM—1表达的影响。结果：脂质体介导的转染方法能将ODNs有效地转染至HUVECs中，且AODNs可有效抑制NF-κB的复制合成。NF—κBP65的AODNs可使TNF—α刺激的人脐静脉内皮VCAM-1mRNA表达下调33．08％，蛋白质水平的表达下调48．27％，并与免疫组织化学染色显示结果一致。结论：NF—κB的AODNs可显著下调NF—κB调控的、与动脉粥样硬化相关的黏附分子表达。     

Insulin-like growth factor-I activates NFκB and NLRP3 inflammatory signalling via ROS in cancer cells

Previous studies have demonstrated that insulin-like growth factor-I (IGF-1) and reactive oxygen species (ROS) are involved in the development and progression of various cancers. However, their regulatory mechanism remains unknown. In this study, we treated cancer cells (HeLa, HepG2 and SW1116 cells) and normal cells (NCM-460) with IGF-1 at different concentrations and for different times and found that cancer cells produced large amounts of cytoplasmic ROS in cancer cells but not in normal cells. Further mechanistic analysis demonstrated that IGF-1 activated NFκB and NLRP3 inflammatory signalling in HeLa cells; systematic analysis indicated that IGF-1 activates NFκB and NLRP3, and the activation was cytosolic ROS- and NADPH oxidase 2 (NOX2)-dependent. Additionally, through coimmunoprecipitation experiments, we found that the IRS-1/COX2/mPGES-1/MAPKs/RAC2/NOX2 pathway nexus was involved in IGF-1-induced NFκB and NLRP3 production. Finally, we validated the regulatory mechanisms through IRS-1, mPGES-1 or NOX2 inhibition using their respective selective inhibitors or shRNA knockdown. Taken together, this is the first report on the mechanism by which IGF-1 activates NFκB and NLRP3 inflammatory signalling via ROS. These findings pave the way for an in-depth study of the role of IGF-1 and ROS in inflammation associated with the development and progression of cancer.     

Btk及NFκB在急性髓系白血病细胞中的表达及其意义

摘要本研究检测Btk及NFκB在急性髓系白血病（AML）患者白血病细胞中的表达,评价其在AML发生、发展中的作用。选取14例AML初诊及治疗达完全缓解患者的骨髓单个核细胞标本,检测Btk、NFκB在mRNA及蛋白质水平的表达。结果表明：在mRNA及蛋白质水平,AML患者细胞中均有Btk、NFκB的表达。Btk、NFκB蛋白在初发AML患者白血病细胞中表达高,达完全缓解后,其表达下降或检测不到（P〈0．05）。结论：Btk、NFκB在AML的发生、发展中可能起重要作用,它们有可能作为AML的潜在治疗靶点及用于预后预测。     

顺铂抑制IL-8诱导人卵巢癌SKOV-3细胞的迁移作用及相关机制的研究

目的 观察外源性人白细胞介素-8 （IL-8）对人卵巢癌SKOV-3细胞迁移的影响,及顺铂对它的干预作用,初步探讨顺铂抑制细胞迁移的机制.方法 顺铂处理SKOV-3细胞,MTT法确定顺铂使用的最佳作用浓度;Transwell法观察顺铂对IL-8诱导SKOV-3细胞迁移的干预作用;ELISA法检测顺铂分泌IL-8情况;Western blot法检测NF-κB蛋白表达水平.结果 MTT结果显示：与对照组相比,顺铂浓度为100μg/ml对细胞增殖有显著抑制作用（P＜0.05）.浓度区间在200～400μg/ml的顺铂对细胞的增殖也有抑制作用,该范围内对细胞的生长抑制率无统计学差异（P＞0.05）.浓度为100μg/ml的顺铂,分别作用于SKOV-3细胞24 h、48 h、72 h,各时间组比较无统计学差异（P＞0.05）.IL-8（100 ng/L）处理细胞后,SKOV-3细胞的迁移能力增强,顺铂（100 μg/ml）具有抑制IL-8诱导的SKOV-3细胞迁移的作用,随着浓度的增高,迁移的细胞数由241.67减少到155.99,差异有统计学意义（P＜0.05）.顺铂刺激细胞后,与空白对照组相比,NF-κB蛋白表达水平降低（64.04±4.6）.结论 IL-8具有促进人卵巢癌SKOV-3细胞迁移的作用,顺铂可能是通过NF-κB细胞信号通路对卵巢癌细胞的迁移起抑制作用.     

核转录因子κB信号通路在应力调控成肌细胞分化中的作用

背景:NF-κB信号通路在细胞生长分化、炎症反应、肿瘤生长等过程中发挥重要的调节作用,也参与成肌细胞分化的调控。目的:分析NF-κB信号通路在应力介导的C2C12成肌细胞分化中的作用及其作用机制。方法:成功构建大鼠C2C12成肌细胞体外培养-力学刺激模型,采用多通道细胞牵张应力加载系统,以0.5Hz的加载频率和10%的细胞拉伸变形幅度对细胞进行拉伸培养2,6,12,24h。结果与结论:①C2C12成肌细胞在周期性机械拉伸力作用下,NF-κB信号通路被激活。当细胞受到应力刺激6h后,胞核NF-κBp65亚基蛋白表达水平开始增强,24h内NF-κBp65亚基蛋白表达水平达到峰值。加力12,24h组与未加力对照组之间差异有显著性意义(P<0.05)。②IκBα蛋白表达水平在加力6h后表达显著下降,24h内IκBα蛋白表达水平减弱达到最低。加力12,24h组与未加力对照组之间差异有显著性意义(P<0.05)。③周期性张应力促进C2C12成肌细胞分化过程中Myogenin的表达,加入NF-κB信号通路特异性抑制剂吡咯烷二硫氨基甲酸(20μmol/L)后再加力,Myogenin的表达明显降低。以上结果提示:①NF-κB信号通路可能参与应力介导的C2C12成肌细胞分化的调控过程。②当细胞受到应力刺激时,胞质IκBα发生磷酸化并降解。③NF-κB信号通路在应力介导的C2C12成肌细胞分化过程中发挥重要作用,但不是这一调控过程的惟一通路。     

Short term exposure to ethyl pyruvate has long term anti-inflammatory effects on microglial cells

Ethyl pyruvate (EP) has been increasingly appreciated as an anti-inflammatory and neuroprotective agent with potent pharmacological properties relevant for treatment of various CNS disorders. Microglial cells seem to be particularly sensitive to its effects. In this study, microglial cells were exposed to EP for relatively short periods (10–120 min) and inflammatory properties of the cells were determined after 24 h of cultivation. Application of EP in the short-term periods inhibited production of interleukin-6, tumor necrosis factor and nitric oxide in microglial cells. At the same time, the effects on cell viability, reactive oxygen species generation and expression of F4/80 and CD40 of microglial cells were minor. NFκB activation was not affected by EP in the cells during the short exposures, thus implying that the observed effect of EP on cytokine and nitric oxide generation was performed in NFκB independent way. Importantly, effects of the short term EP treatment on microglial cells were detected by a real time cell analysis, as well. The observed ability of EP to affect microglial cell function after relatively short time of exposure is relevant for its therapeutic potential against inflammatory disorders of the CNS.     

Inflammatory and protein metabolism signaling responses in human skeletal muscle after burn injury

Severe burn injuries lead to a prolonged hypercatabolic state resulting in dramatic loss of skeletal muscle mass. Postburn muscle loss is well documented but the molecular signaling cascade preceding atrophy is not. The purpose of this study is to determine the response to burn injury of signaling pathways driving muscle inflammation and protein metabolism. Muscle biopsies were collected in the early flow phase after burn injury from the vastus lateralis of a noninjured leg in patients with 20 to 60% TBSA burns and compared with uninjured, matched controls. Circulating levels of proinflammatory cytokines were also compared. Immunoblotting was performed to determine the protein levels of key signaling components for translation initiation, proteolysis, and tumor necrosis factor/nuclear factor kappa B (NFκB)and interleukin (IL)-6/STAT3 signaling. Burn subjects had significantly higher levels of circulating proinflammatory cytokines, with no difference in muscle STAT3 activity and lower NFκB activity. No differences were found in any translational signaling components. Regarding proteolytic signaling in burn, calpain-2 was 47% higher, calpastatin tended to be lower, and total ubiquitination was substantially higher. Surprisingly, a systemic proinflammatory response 3 to 10 days postburn did not lead to elevated muscle STAT3 or NFκB signaling. Signaling molecules governing translation initiation were unaffected, whereas indices of calcium-mediated proteolysis and ubiquitin-proteasome activity were upregulated. These novel findings are the first in humans to suggest that the net catabolic effect of burn injury in skeletal muscle (ie, atrophy) may be mediated, at least during the early flow phase, almost entirely by an increased proteolytic activity in the absence of suppressed protein synthesis signaling.     

Pulsed ultrasound and dimethylsulfoxide gel treatment reduces the expression of pro-inflammatory molecules in an animal model of muscle injury

Studies have shown an exacerbated increase in proinflammatory markers during and after muscle injury. In this way, interventions that reduce inflammatory activation appear to be of great interest in muscle injury therapy. Thus, the preset study evaluated the effect of low-intensity pulsed ultrasound (LIPUS) and dimethylsulfoxide (DMSO) on the proinflammatory molecules in an animal model of traumatic muscle injury. Forty-eight 3-month old male Wistar rats were divided into six groups (n = 8/group): sham; muscle injury without treatment; muscle injury and gel-saline (0.9%); muscle injury and gel-DMSO (15 mg/kg); muscle injury and LIPUS plus gel-saline; and muscle injury and LIPUS plus gel-DMSO. Two, 12, 24 and 48 h after trauma, four groups received one of the treatments described. One hour after, Western blot was performed to quantify proinflammatory protein levels. We observed greater protein levels of TNFα (3.9 times), IL-1β (3.6 times), JNK phosphorylation (4.2 times) and NFκB (3.8 times) in muscle injury group. However, the combined LIPUS with DMSO resulted in significantly lower levels of TNFα (2.2 times), IL-1β (2.1 times), JNK phosphorylation (2.4 times), and NFκB (2.1 times). The results demonstrate that LIPUS associated with DMSO gel can attenuate TNFα, IL-1β, NFκB protein levels and JNK phosphorylation in traumatic muscle injury.