酪氨酸激酶信号级联与支气管哮喘发病的关系

支气管哮喘的发病机制涉及炎症细胞和气道结构细胞、细胞因子、趋化因子、生长因子和炎症介质的相互作用。酪氨酸激酶信号级联在变应性气道炎症中起重要作用，活化的酪氨酸激酶激活了多重下游信号转导途径如磷酯酰肌醇3激酶、丝裂原活化蛋白激酶和核因子κB，导致细胞的分化、存活、增殖、脱颗粒和趋化。     

Imatinib治疗胃肠道基底细胞癌疗效与安全性评价

如众所知,KIT酪氨酸激酶受体持续活化在胃肠道基底细胞癌发病中起关键作用。临床前期研究表明,选择性酪氨酸激酶受体抑制剂Imatinib对治疗胃肠道基底细胞癌可能有益。本文拟就Imatinib治疗胃肠道基底细胞癌相关药效与安全性进行了评估。对象与方法 147例重度胃肠道基底细胞癌患者,其中144例(98％)已接受过手术治疗,75例(51％)因手术无法根治或肿瘤转移而接受过化学药物治疗,22例(15％)接受     

粘附斑激酶家族新成员Pyk2的研究进展

富含脯氨酸的酪氨酸激酶2（proline—rich tyrosine kinase 2，Pyk2），又称细胞粘附激酶β（CAKβ）、相关粘附聚焦酪氨酸激酶（RAFTK），是粘附斑激酶（focal adhesion kinase．FAK）家族的新成员，与FAK具有高度同源性。Pyk2活化可催化多种含SH2结构域的底物蛋白磷酸化，涉及到多条信号传导通路，包括离子通道的调节、细胞生长增殖分化和细胞洲亡等，但其功能机制至今尚不清楚。     

Tyro3受体酪氨酸激酶参与类风湿关节炎发病的研究进展

Tyro3受体酪氨酸激酶（Tyro3TK）属于受体酪氨酸激酶TAM（Tyro3/Axl/Mer）家族中的一员,其可表达在多种细胞表面并且主要通过配体介导的方式激活,活化后的Tyro3 TK能够启动下游的不同信号转导通路进而影响多种生物学功能。研究发现,Tyro3 TK可通过参与凋亡细胞吞噬和调节炎症反应等方式在免疫调控...     

TAM受体酪氨酸激酶与肾脏疾病

TAM(TYRO3、AXL、MER)受体酪氨酸激酶(TAM-RTKs)属广泛表达的受体酪氨酸激酶亚家族,在细胞增殖、生存、迁移、胞葬、炎症及免疫调控、血小板稳定等多方面发挥重要功能。动物模型研究发现,肾脏局部或全身的TAM-RTKs功能异常广泛参与Thy1肾小球肾炎、糖尿病肾病、抗肾小球基膜肾炎、单侧输尿管梗阻、肾毒性血清肾炎、急性肾损伤、高血压肾损伤等肾脏疾病的发病机制中。此外,肾脏TAM-RTKs及循环中分泌型TAM-RTKs的水平同狼疮性肾炎、糖尿病肾病、慢性肾脏病等疾病严重程度存在关联,有望成为新型疾病分子标志物。TAM-RTKs亦参与慢性肾脏病相关血管粥样硬化及钙化的过程中。本文将对TAM-RTKs在肾脏疾病中的研究进展进行综述。     

JAK/STAT 信号通路在肺纤维化中作用的研究进展

蛋白酪氨酸激酶(JAK)/信号转导转录激活因子(STAT)信号通路是介导炎症反应的重要信号通路之一,广泛参与细胞的增生、分化、凋亡、免疫调节等病理生理过程。JAK/STAT 信号通路通过介导肺巨噬细胞、成纤维细胞、肺泡上皮细胞的病理性活化及损伤,对肺纤维化进程具有重要调控作用。此文就 JAK/STAT 信号通路在肺纤维化中的作用机制及研究进展作一综述。     

脑老化与阿尔茨海默病中神经生长因子及其受体变化的研究进展

神经生长因子不仅在神经元的胚胎期和发育期，而且在某些成熟的神经元中也有重要的营养支持作用。神经生长因子有高亲和力酪氨酸激酶和低亲和力ｐ７５二种受体。酪氨酸激酶Ａ受体介导的存活信号途径与ｐ７５受体介导的凋亡途径相互制约、平衡。目前研究已观察到在脑退行性病变如脑老化、阿尔茨海默病中神经生长因子ｍＲＮＡ的表达和神经生长因子蛋白量无减少或少量增加，而酪氨酸激酶ＡｍＲＮＡ减少，ｐ７５ｍＲＮＡ增加。因此通过提     

急性髓系白血病的FMS样酪氨酸激酶3的研究和临床意义

FMS样酪氨酸激酶3(FLT3),是Ⅲ型酪氨酸激酶受体(RTKⅢ)的一种,优先表达在定向造血干细胞的细胞表面,与FLT3配体(FL)的相互作用在造血过程的维持,增殖和分化中发挥重要作用。FLT3基因的活性突变是急性髓系白血病(AML)最常见的基因损伤,而且FLT3基因突变通常会给AML患者带来更差的预后。临床上大约30%的AML患者以及少量的急性淋巴细胞白血病(ALL)患者以及骨髓增生异常综合征(MDS)患者发现了FLT3基因的突变。研究FLT3基因突变如何引起基因自身活化和不受机体控制的信号转导的作用机制可能会对突变的FLT3基因如何变成致癌基因…     

肝癌与细胞内信息传递

细胞生长和分化等生命基本活动所必需的蛋白质酪氨酸磷酸化过程是由蛋白质酪氨酸激酶(protein tyrosine kinases PTKs)和蛋白质酪氨酸磷酸酶(protein tyrosine phosphatases,PTPs)之间的协调作用所决定。细胞信息传递过程中,根据细胞的反应不同,PTKs和PTPs相互间发生拮抗和协同作用,而两者之间的平衡失调,可影响正常细胞的生长并与细胞发生恶性转化有关。自1980年Hunter研究Rous肉瘤病毒致痛机理时发现癌基因Src的表达产物具有PTKs活性以来,认识到蛋白质酪氨酸磷酸化过程对细胞的增殖、分化和癌变有直接的关系。肝细胞各种促分裂因子的受体大部分是通过酪氨酸激酶传递信息,就此对酪氨酸介导的细胞内信息传递与肝细胞的增殖、癌变的关系作一概述。     

蛋白—酪氨酸激酶在大鼠血管平滑肌细胞诱导型一氧化氮合酶基 …

为了解蛋白－酪氨酸激酶及蛋白激酶Ｃ在血管平滑肌细胞诱导型一氧化氮合酶基因表达的作用,应用蛋白－酪氨酸激酶抑制剂抑制细胞蛋白－酪氨酸激酶活性及应用伏波脂耗竭细胞蛋白激酶Ｃ。     

支气管哮喘患者Rho激酶信号通道与T调节细胞的相关性

支气管哮喘（简称哮喘）被认为是一种气道慢性非特异性炎症性疾病,许多细胞因子和炎症介质参与了这个病理生理过程。目前研究显示,Rho激酶信号通道及T调节细胞在哮喘的发病机制中起重要作用,而他汀类药物也具有抑制促炎性细胞因子和细胞因子的分泌,增加调节性T细胞数量和功能等作用。本文就哮喘中Rho激酶信号转导通路与调节T细胞的相关性进行简要综述。     

白介素17A及其在支气管哮喘中的作用

白介素17A（interleukin-17A,IL-17A）是近年来发现的一种由Th17等多种细胞产生的细胞因子,可以通过不同途径调节微环境中细胞因子、趋化因子、黏附性分子的表达,募集炎症细胞特别是中性粒细胞而发挥炎症效应,参与炎症性疾病。支气管哮喘（简称哮喘）是由多种炎症因子参与的慢性气道炎症性疾病,不断有证据表明IL-17A参与哮喘的发病过程。本文就IL-17A的来源及其在哮喘特别是中性粒细胞炎症性哮喘的气道炎症、气道高反应性、气道重塑及激素治疗抵抗中发挥的作用及机制加以综述。     

Airway smooth muscle cells: contributing to and regulating airway mucosal inflammation?

In addition to its contractile properties, airway smooth muscle may contribute to the pathogenesis of asthma by increased proliferation, and by the expression and secretion of pro-inflammatory cytokines and mediators. Studies of airway smooth muscle cells in culture have shown that many mitogenic mediators can induce proliferation, and that these may therefore, contribute to the increase in airway smooth muscle mass observed in asthma. Other mechanisms for airway smooth muscle proliferation include the interaction with inflammatory cells such as T-cells and eosinophils. Airway smooth muscle cells may also be a source of inflammatory mediators and cytokines, in particular chemokines, thus implicating airway smooth muscle cells as contributors to the inflammatory mechanisms of asthma. The pro-activating signals for converting airway smooth muscle cells into a proliferative and secretory cell in asthma are unknown, but may include viruses and immunoglobulin E. Airway smooth muscle contractility may also be altered in response to inflammation. Airway smooth muscle cells may play an important interactive role with inflammatory and other structural cells, contributing to inflammation, injury and repair of the airways. Such a recognition makes it imperative to consider the airway smooth muscle as a target of therapeutic drugs for suppressing not only the contractile but also the proliferative and secretory effects of asthma.     

上皮源性细胞因子与支气管哮喘

支气管哮喘(简称哮喘)是全球最常见的慢性气道炎症性疾病之一.慢性气道炎症是哮喘的内在发病机制,炎症细胞在气道的局部聚集、炎症介质和细胞因子的释放促使气道炎症发生.上皮源性细胞因子是免疫活性细胞的效应因子,其免疫调节功能在哮喘发病机制中处于中心地位.在人类肺组织及免疫细胞中,细胞因子的表达增高,从而导致肺部变态反应性疾病的发生.近年来利用哮喘发病机制中细胞因子作为靶点进行靶向治疗哮喘已成为未来哮喘治疗研究的主要热点.本文主要就上皮源性细胞因子中IL-25、IL-33及胸腺基质淋巴细胞生成素的结构和功能进行介绍,并对其与哮喘的关系作一简单综述.     

Reactive Oxygen Species as Mediators in Asthma

This review describes production and effects of reactive oxygen species (ROS) on airway function. ROS are important in many physiological processes but can also have detrimental effects on airway cells and tissues when produced in high quantities or during the absence of sufficient amounts of anti-oxidants. Therefore, these mediators play a prominent role in the pathogenesis of various inflammatory airway disorders, including asthma. Effects of ROS on airway function in asthma have been studied with isolated airway cells and tissues and with animal models and patients. With the use of inhibitors, transgenic animals and measurements of the release of ROS within the airways, it became clear that oxidative stress contributes to the initiation and worsening of inflammatory respiratory disorders.     

Role of airway epithelial cells in development of asthma and allergic rhinitis

Asthma and allergic rhinitis frequently coexist in the same patient. There is a similarity and variation as well as potential relationship between asthma and allergic rhinitis. There is an increasing evidence to suggest a major involvement of airway epithelial cells in the pathogenesis of asthma and allergic rhinitis. The present review describes the importance of the airway epithelial cell in the development of allergic airway diseases, its role as the primary airway defense against exposure of the airway and lung to inflammatory stimuli and antigens and as an important player through activation of epithelial Toll-like receptors (TLRs) to provide an important link between innate immunity and allergic disease. Additionally, airway epithelial cells can act as inflammatory promoters capable of directing dendritic cells (DCs) towards a T helper 2 (Th2) response, and as active producers of several inflammatory/anti-inflammatory mediators. It is hypothesized that airway epithelial cells may play as both inflammatory initiator and immuno-pathological feedback regulation between allergic rhinitis and asthma via release of systemic inflammatory mediators. Thus, airway epithelial cells may be valuable therapeutic targets for discovery and development of new drugs and/or new therapeutic strategies to treat asthma and allergic rhinitis.     

Matrix Metalloproteinases in the Pathogenesis of Asthma and COPD

While asthma is an inflammatory disorder of the airways involving mediators released from mast cells and eosinophils, inflammation alone is insufficient to explain the chronic nature of the disease. Recent progress in the understanding of disease pathogenesis has revealed that airway remodeling, which is at least in part due to an excess of extracellular matrix (ECM) deposition in the airway wall, plays a significant role in airflow obstruction. Matrix metalloproteinases (MMPs) have been suggested to be the major proteolytic enzymes to induce airway remodeling in asthma and COPD. It has been widely accepted that different inflammatory processes are involved in asthma and COPD with different inflammatory cells, mediators, and responses to treatments. Despite these different processes, airflow obstruction and airway remodeling characterize these two diseases. MMP-2 and -9 have been reported to be involved in the pathogenesis of airway remodeling in both diseases and MMP-12, in addition to these MMPs, in the pathogenesis of COPD. In this review, we discuss the current views on the role of MMPs in the pathogenesis of bronchial asthma and COPD. Anti-MMP therapy could theoretically be useful to prevent airway remodeling in asthma and COPD. However, to date no clinical data are available regarding the efficacy of anti-MMP therapies in the treatment of patients with asthma and COPD.     

Asthma: emerging concepts and potential therapies

Asthma is a disease of the airways that results in reversible airflow obstruction. Recent investigations have suggested that airway inflammation is associated with increased airway responsiveness and worsening of asthmatic symptoms. The role that mast cell mediators might play in the production of asthma has been investigated by use of newer analytical techniques and by use of fiberoptic bronchoscopy with lavage to obtain lower respiratory tract fluid and cells. In addition, new investigational compounds that interfere with the synthesis or action of inflammatory mediators have been tested. Developing lines of investigation suggest that chronic activation of inflammatory cells may be important in the pathogenesis of asthma.     

肥大细胞Toll样受体在支气管哮喘中的作用研究进展

支气管哮喘是一种慢性气道炎症性疾病,其病理生理特征主要表现为可逆性的气流受限和气道高反应性。其中嗜酸粒细胞、肥大细胞、中性粒细胞等是气道炎症的主要效应细胞。本文介绍了肥大细胞的来源、分型以及活化后释放的介质种类。重点综述了肥大细胞上Toll样受体的种类、作用以及在支气管哮喘的发生发展中的作用。