缺氧复氧诱导神经细胞焦亡的研究进展

细胞焦亡是一种有别于凋亡的促炎程序性细胞死亡方式,分为依赖于半胱氨酸天冬氨酸蛋白酶-1(caspase-1)介导的经典炎症小体途径和依赖于半胱氨酸天冬氨酸蛋白酶-4/5/11(caspase-4/5/11)介导的非经典炎症小体途径。多项研究表明,caspase-1依赖的经典炎症小体途径在缺氧复氧诱导神经细胞焦亡中扮演了重要角色,上游多种因素可以对该焦亡途径进行调控。本文对此研究进展作一概括。     

炎症小体及细胞焦亡在肠道稳态中的研究进展

炎症小体是一种细胞内多蛋白复合物,主要包括NLRP3、AIM2、NLRP6、NLRP12等亚型。识别相关刺激后,炎症小体进行组装并激活caspase-1,激活的caspase-1促进IL-1β和IL-18成熟和分泌。另外,活化的caspase-1也可裂解gasdermin D(GSDMD),导致特殊形式的细胞死亡——细胞焦亡。肠道稳态在维持机体健康中起重要作用,而炎症小体及细胞焦亡通路在肠道稳态维持中发挥重要作用。本文主要阐述炎症小体及细胞焦亡在肠道稳态维持中的最新研究进展。     

泛连接蛋白1参与炎症调控及细胞焦亡的研究进展

<正>1泛连接蛋白1(pannexin 1, Panx1)通道及其调控1.1 Panx1概况Panx1作为泛连接蛋白家族成员之一,激活后可在细胞膜上形成通道,释放10 kD以内的物质于细胞外,如腺苷三磷酸(adenosine triphosphate,ATP)、尿苷三磷酸(uridine triphosphate, UTP)、K⁺和Ca²⁺等。细胞内物质作为炎症介质,经Panx1释放到细胞外,诱导失控性炎症反应发生^[1]。     

细胞焦亡:一种新的细胞死亡方式

细胞焦亡是近年来发现并证实的一种新的程序性细胞死亡方式,其特征为依赖于半胱天冬酶-1(caspase-1),并伴有大量促炎症因子的释放.细胞焦亡的形态学特征、发生及调控机制等均不同于凋亡、坏死等其他细胞死亡方式.研究表明,细胞焦亡广泛参与感染性疾病、神经系统相关疾病和动脉粥样硬化性疾病等的发生发展,并发挥重要作用.对细...     

细胞焦亡与肾脏疾病

细胞焦亡是一种区别于细胞凋亡的病理性自杀方式,主要由半胱氨酸蛋白酶1（Caspase-1）和/或半胱氨酸蛋白酶4/5/11（Caspase-4/5/11）依赖性介导,伴随产生大量炎性因子,致使细胞程序性死亡。细胞焦亡信号传导途径主要包括经典焦亡途径和非经典焦亡途径,炎性小体生成和打孔蛋白Gasdermin D（GSDM...     

炎症小体介导细胞焦亡和自噬的相关研究

炎症小体是大型多蛋白复合物,其激活参与各种自身炎症和自身免疫性疾病病理过程。半胱天冬酶1(caspase-1)介导的炎症小体通路受病原微生物和无菌应激物激活,分泌促炎细胞因子IL-1β和IL-18,广泛参与各种慢性疾病的进展,如动脉粥样硬化、2型糖尿病、阿尔兹海默病以及关节炎等。在分子生物学层面,各类炎症小体则在维持机体自身免疫功能和调节细胞焦亡自噬方面发挥重要作用。     

IL-1β调控细胞焦亡分子通路对创伤性脑损伤大鼠血脑屏障损伤的影响

目的 探讨IL-1β调控细胞焦亡分子通路对创伤性脑损伤(TBI)大鼠血脑屏障(BBB)损伤的影响机制.方法 8周龄Balb/c雌性SD大鼠分为对照组不作任何处理,假手术组未接受自由落体外力击打,TBI组构建完整模型,比较各组脑组织BBB情况、BBB内皮细胞分子NIRP1、NIRP3、caspase-1、IL-1β、IL-18表达水平.构建BBB体外模型,IL-1β刺激后检测BBB内皮细胞分子表达水平、TUNEL法检测细胞焦亡情况、免疫沉淀技术检测IL-1β对caspase-1的调控作用.结果 3、6、12、24、48、72 h时,TBI组脑组织EB浓度均高于对照组、假手术组(P<0.05),对照组和假手术组脑组织EB浓度比较差异无统计学意义(P>0.05);与对照组比较,假手术组NIRP1、NIRP3、caspase-1、IL-1β、IL-18表达差异无统计学意义(P>0.05),TBI组NIRP1、NIRP3、caspase-1、IL-1β、IL-18表达水平显著升高(P<0.05).BBB组NIRP1、NIRP3、caspase-1、IL-1β、IL-18表达水平高于非BBB组(P<0.05),IL-1β组NIRP1、NIRP3、caspase-1、IL-1β、IL-18表达水平高于BBB组(P<0.05);IL-1β组TUNEL阳性细胞多于对照组(P<0.05).IL-1β、IL-1βsiRNA与caspase-1共转染小鼠细胞,结果IL-1β组荧光活性低于IL-1βsiRNA组(P<0.05),IL-1β组和caspase-1组荧光活性差异无统计学意义(P>0.05).结论 IL-1β可通过调控细胞焦亡,引起炎症因子表达上调和细胞焦亡分子上调,升高TBI后大鼠BBB的炎症反应,促进了TBI后BBB损伤.     

细胞焦亡及相关疾病的研究进展

细胞焦亡是由Gasdermin蛋白介导的一种程序性炎性细胞死亡方式,分为依赖caspase-1的经典途径和依赖caspase-4/5/11的非经典途径。炎性小体的激活在此过程中扮演重要角色。细胞焦亡参与肾脏疾病、动脉粥样硬化、神经系统疾病、感染性疾病等的发生发展,并发挥重要作用。通过对细胞焦亡作用机制及相关疾病的研究,为临床疾病的防治提供新思路。     

细胞焦亡在肾脏炎性损伤中的作用研究进展

细胞焦亡(pyroptoysis)是由活化的caspase-1触发的一种特殊的细胞程序性死亡。肾脏细胞焦亡在肾损伤中发挥着重要的作用。GSDMD切割焦亡关键蛋白caspase-1引起下游炎性反应因子IL-18,IL-1β的成熟和释放引起肾脏炎性反应和细胞焦亡发生。本文从NLRP3激活导致肾脏炎性反应、GSDMD裂解引发细胞焦亡等角度,阐释NLRP3-caspase-1-GSDMD介导的细胞焦亡在肾脏炎性反应中的作用。     

IL-33/ST2信号通路在纤维化疾病中的作用

Interleukin (IL)-33 is a member of IL-1 family. It is identified as a functional ligand for ST2 which is an IL-1 receptor-like protein. IL-33/ST2 signaling is involved in T-cell-mediated immune responses. Increasing evidence indicates that IL-33 has different roles in different diseases. Recently, some studies have demonstrated that IL-33 may be related to the genesis and development of fibrosis diseases. We review current knowledge of the biological characteristics of IL-33 and the role of IL-33/ST2 signaling pathway in fibrosis diseases.     

IL-17, 18, 23, 25在变态反应性疾病中的作用

Many newly discovered interleukins have been implicated to play an important role in the pathogenesis of the allergic diseases, for example, human intedeukin [IL) - 17, a T- cell derived cytokine;intedeukin (IL) - 18, an interferon (IFN) - gamma - inducing cytokine; interleukin (IL) - 23, produced by activated dendritic cells, and interleukin (IL) -25, a recently described T helper 2 (Th2) cell- derived cytokine. Understanding their characteristic and roles in diseases may help us to know better the mechanism of the allergic diseases and develop the strategy for treating the disease.     

长链非编码RNA对心脏发育的表观遗传学调控研究进展

<正>长链非编码RNA(long noncoding RNA or large noncoding RNA,lncRNAs)是一类转录本长度超过200 nt的功能性RNA,存在于细胞核或胞质中。lncRNAs能调节生命过程中关键基因的表达,从而影响机体正常生理发育、功能维持和异常病理过程,如神经干细胞分化发育、心脏疾病发生、肿瘤形成[]     

焦亡信号通路炎症小体与中枢神经系统疾病研究进展

焦亡是一种新发现并证实与炎症相关的细胞死亡方式,其特征为依赖于半胱天冬氨酸蛋白酶-1(caspase-1)的细胞程序性死亡,并伴有促炎症因子的释放,主要为白细胞介素1β和IL-18.虽然焦亡与坏死和凋亡有相似之处,但它们是迥然不同的生物学过程.越来越多的研究发现,焦亡相关信号通路在中枢神经系统疾病中起重要作用,包括急性脑感染、神经变性疾病、急性无菌性脑损伤和慢性无菌性中枢神经系统炎症.     

NLRP3炎性小体激活调控机制研究新进展

NLRP3炎性小体是一种胞内多蛋白复合体,主要由NOD样受体家族成员NLRP3、接头蛋白ASC以及前体半胱天冬酶1(pro-caspase-1)组成,该炎性小体可以通过激活caspase-1促进促炎因子白细胞介素-1 beta(IL-1β)和IL-18的分泌以及细胞焦亡(pyroptosis)的形成.NLRP3炎性小体的激活在很多自身免疫性及自身炎症性疾病中扮演着重要的角色,因此,深入探究NLRP3炎性小体激活的调控机制可为NLRP3炎性小体相关疾病的治疗提供更多新的思路.     

Interleukin-1β in innate inflammation,autophagy and immunity

Although IL-1β is the master inflammatory cytokine in the IL-1 family, after more than ten years of continuous breeding, mice deficient in IL-1β exhibit no spontaneous disease. Therefore, one concludes that IL-1β is not needed for homeostasis. However, IL-1β-deficient mice are protected against local and systemic inflammation due to live infections, autoimmune processes, tumor metastasis and even chemical carcinogenesis. Based on a large number of preclinical studies, blocking IL-1β activity in humans with a broad spectrum of inflammatory conditions has reduced disease severity and for many, has lifted the burden of disease. Rare and common diseases are controlled by blocking IL-1β. Immunologically, IL-1β is a natural adjuvant for responses to antigen. Alone, IL-1β is not a growth factor for lymphocytes; rather in antigen activated immunocompetent cells, blocking IL-1 reduces IL-17 production. IL-1β markedly increases in the expansion of naive and memory CD4T cells in response to challenge with their cognate antigen. The response occurs when only specific CD4T cells respond to IL-1β and not to IL-6 or CD-28. A role for autophagy in production of IL-1β has emerged with deletion of the autophagy gene ATG16L1. Macrophages from ATG16L1-deficient mice produce higher levels of IL-1β after stimulation with TLR4 ligands via a mechanism of caspase-1 activation. The implications for increased IL-1β release in persons with defective autophagy may have clinical importance for disease.     

一个新的Wnt信号通路相关蛋白——Rspo3

Wnt信号通路是生物体中最重要的信号通路之一,其在胚胎和成体中控制细胞的增殖、分化以及形态发生.R-spondin(Rspo)家族是一个近年来新发现的蛋白家族,由4个分泌性蛋白Rspo1 ～4组成.Rspo蛋白家族成员均有两个富含半胱氨酸的furin-like结构域,一个TSP1结构域和一段富含碱性氨基酸的C端区域.已...     

IL-1β和IL-18在鼠巨细胞病毒播散性感染中的表达及意义

目的:在整体水平观察鼠巨细胞病毒(Murine cytomegalovirus,MCMV)播散性感染时脏器病毒载量、caspase-1的活化及其下游因子IL-1β和IL-18的表达状况。方法:建立MCMV播散性感染模型,MCMV Smith株接种后第0、3、7和14天各处死4只小鼠;同时设模拟感染小鼠作为对照。标准空斑试验检测唾液腺、肺和肝组织病毒滴度;Western blot法检测脾细胞中procaspase-1及其活化形式caspase-1的表达强度;双抗体夹心ELISA法检测血清IL-1β和IL-18水平;免疫组化法检测唾液腺、肺和肝组织中IL-1β和IL-18表达状况。结果:肝组织病毒滴度于MCMV感染后3天升高,其后迅速减低,感染2周内肺组织中未检测到病毒,而唾液腺组织病毒滴度呈逐渐增高趋势;与模拟感染对照组比较,播散性感染组感染后3天脾细胞中procaspase-1和caspase-1的表达明显升高(相对吸光值均P<0.01);同时,血清IL-1β和IL-18水平升高达峰值(均P<0.01)。结论:MCMV感染后炎性体活化,caspase-1表达升高;其下游信号IL-1β和IL-18成熟释放增加,并呈组织差异性表达。     

Histochemically demonstrable monoamine oxidase activity in the adult human heart in various cardiac diseases

Summary The present work was undertaken in order to study the role of monoamine oxidase (MAO) enzyme in the genesis of altered cardiac noradrenalin level in the human heart in various underlying pathologic conditions. The histochemical localization and the activity of MAO were studied in the right atrial appendage of man in ischemic heart disease, in valvular heart disease without or with congestive myocardial failure, and in hearts with an uncomplicated atrial septal defect.MAO was found to be localized mainly extraneuronally in the muscle cells, a little activity was detected in the connective tissue spaces, and nerves reacting positively were tentatively identified. There were no significant differences in MAO activity measured photometrically between the various heart disease groups. It seems that MAO enzyme plays only a small or no role in the genesis of the altered noradrenalin level in the human heart observed in ischemic heart disease or congestive cardiac failure.