IL-33通过调节NF-κB信号通路促进肝癌细胞增殖和迁移

目的 探讨IL-33通过对NF-κB信号通路及炎症因子的调控,对肝癌HepG2细胞增殖和迁移的影响。方法 RT-PCR检测IL-33在不同肝癌细胞系中的表达,Western Blot检测IL-33对HepG2细胞NF-κB信号通路激活相关蛋白(NF-κB、p-NF-κB、IKB、p-IKB)的调控,ELISA检测IL-33对HepG2细胞中IL-1α、IL-1β、IL-6、IL-18等炎症因子释放的调控,EdU增殖实验检测IL-33对HepG2细胞增殖的影响,CCK8实验检测IL-33对HepG2细胞24 h和48 h活力的影响,Transwell小室实验和划痕实验检测IL-33对HepG2细胞迁移的影响。结果 IL-33 mRNA表达分别为LO2(1.01±0.01)、MHCC97H(1.08±0.05)、LM3(1.76±0.21)、HepG2(3.88±0.35)、SMCC7721(2.24±0.43)和Hep3B(2.13±0.30),差异有统计学意义(F=19.621,P=0.001)。IL-33处理24 h组中IL-1α(3185.25±194.67)、IL-1β(2103...     

白细胞介素-33/ST2信号转导通路研究进展

白细胞介素-33(IL-33)是近年发现的IL-1家族新成员,其受体是IL-1受体家族成员ST2.自身免疫性疾病、变态反应性疾病和心血管疾病的研究表明,IL-33是炎性因子,可促进辅助性T细胞(Th2)的产生,参与炎症和免疫反应.此文就IL-33、ST2的生物学特点、IL-33/ST2信号转导通路及其在炎症性肠病、类风...     

IL-33/ST2信号通路在感染性疾病中的研究进展

白细胞介素33(IL-33)是2005年新发现的IL-1家族细胞因子。IL-33通过与其受体肿瘤发生抑制蛋白2(ST2)特异性结合发挥生物学作用,这一过程通常被称为IL-33/ST2信号通路。在不同感染性疾病中,IL-33/ST2信号通路因病原体种类、涉及器官、感染阶段(急、慢性)和免疫微环境等不同而发挥不同的作用。本文综述了IL-33/ST2信号通路在细菌、病毒、真菌和寄生虫等所致感染性疾病中的作用。     

白细胞介素-33与消化系疾病的研究进展

<正>IL-33作为一个新的细胞因子正在为人们所认识,它在疾病发生、发展的过程中起着不同的作用。1白细胞介素(IL)-33的结构和功能IL-33是2003年发现的一个细胞因子,其基因定位于9号染色体(9p24.1),IL-33蛋白主要由270个氨基酸组成。IL-33是一种Th2型辅助因子,但目前认为其可以促进Th1型免疫反应,也可以诱导IL-1和IL-18的分泌。因此IL-33是一种双重     

IL-33生物学特征及其在变应性鼻炎中作用的研究进展

白介素33(interleukin 33,IL-33)是近年发现的第11号IL-1家族成员的双效型细胞因子。IL-33结合具有TIR(Toll/IL-1R)样结构的ST2L受体后激活NF-κB、MAP激酶等信号因子,强有力地促进Th2型细胞因子和趋化因子的释放,在变应性鼻炎(allergic rhinitis,AR)中发挥重要作用。该文对IL-33的生物学特征及其在AR中作用的研究进展进行综述。     

白细胞介素-33抑制脂多糖诱导的心脏微血管内皮细胞通透性的研究初探

目的:探讨白细胞介素-33（IL-33）对脂多糖（LPS）诱导的大鼠心脏微血管内皮细胞（RCMECs）通透性的影响。方法:体外培养RCMECs,分为空白对照组、LPS组、IL-33组和LPS+IL-33组。用细胞计数试剂（CCK8）检测IL-33对RCMECs增殖的影响。异硫氰酸荧光素（FITC）-葡聚糖法检测4组单层...     

类风湿关节炎患者血清白细胞介素-33水平与疾病进程的相关性

目的通过检测类风湿关节炎(RA)患者血清中白细胞介素(IL)-33水平,分析血清IL-33水平与RA的临床及实验室指标之间的相关性,验证IL-33参与RA的发病过程,探讨IL-33对于RA的临床意义。方法采用ELISA方法测定70例RA患者和30例健康对照者血清IL-33水平。结果 RA组血清IL-33水平为(231±335)pg/ml,高于健康对照组(6±23)pg/ml,P<0.01。高疾病活动度组血清IL-33水平为(351±391)pg/ml,高于中低疾病活动度组(145±266)pg/ml,P<0.05。RA患者血清IL-33水平与类风湿因子(RF)及抗环瓜氨酸肽(CCP)抗体呈正相关(P<0.01)。结论 IL-33参与了RA的发病过程,IL-33的升高可能提示RA预后不良。     

白介素33与支气管哮喘

白介素33（IL-33）是2005年被发现的-个新的白介素家族成员。1989年ST2首先被Tominaga鉴定为IL-1受体超家族的-个成员。后来Baekkevold等从高壁内皮细胞中分离得到IL-33分子嘲,而且该分子定位于高壁内皮细胞的核内,故最初被称为“高壁内皮细胞来源的核因子”。直到2005年Schmitz等嘲发现高壁内皮细胞来源的核因子是ST2的特异性配体,并重新命名为IL-33。从那以后人们对IL-33的生物学特征有了更深入的了解。II,-33与ST2结合,诱导Th2细胞因子的产生,从而参与支气管哮喘等Th2相关疾病。本文就IL-33的分子结构、表达、生物学活性及其目前在支气管哮喘发病机制中的作用综述如下。     

白细胞介素33在支气管哮喘急性加重中的作用

支气管哮喘是常见的慢性呼吸道疾病, 大多数情况下哮喘急性发作与接触过敏原、病毒性上呼吸道感染、空气污染、吸烟相关。白细胞介素33(IL-33)是IL-1的家族成员, 从基因、动物实验模型、临床上均已证明IL-33与哮喘密切相关。肺组织中的结构细胞以及被趋化因子招募至肺组织的游离细胞通过一系列模式识别受体、传导介质、传导轴, 诱导IL-33的产生、释放, 进一步导致辅助型T细胞1型免疫反应减弱、辅助型T细胞2型免疫反应增强, 哮喘症状加重。阐明IL-33的释放机制可以为认识哮喘急性发作及精准靶向治疗支气管哮喘提供新的思路。本文对支气管哮喘急性加重过程中IL-33的产生、释放机制作一综述。     

IL-33/ST2轴在呼吸道病毒感染免疫中的作用

IL-33是 IL-1家族的新成员,它能通过结合 IL-1受体家族中的孤儿受体 ST2发挥其生物学效应。很多研究证实呼吸道病毒感染可刺激机体多种细胞显著表达及分泌 IL-33,IL-33作用于靶细胞表面 ST2受体,从而启动 T 辅助细胞(T helper,Th)2型免疫反应,介导呼吸道病毒感染相关疾病。抗 IL-33抗体或抗 ST2抗体阻断 IL-33/ST2轴及上述免疫反应,从而有可能为治疗呼吸道病毒感染相关疾病提供新靶点。     

冠心病与白细胞介素-1受体拮抗剂基因多态性的相关性研究

目的　探讨白细胞介素 1受体拮抗剂基因 (interleukin 1receptorantagonistgene ,IL 1RN)第 2号外显子 +80 0 6T C位点基因多态性在冠心病及正常人群中的分布 ,初步分析其基因型与冠心病的相关关系。方法　采用聚合酶链反应 限制性片段长度多态性的方法 ,检测了 2 40例老年冠心病患者 (冠心病组 )和 2 2 9例老年健康对照者 (对照组 )的IL 1RN(+80 0 6T C)位点基因多态性。结果　对照组和冠心病组的 3种基因型频率分别为TT型 :0 .82 1和 0 .90 0 ;TC型 :0 .170和 0 .0 96 ;CC型 :0 .0 0 9和 0 .0 0 4。与对照组比较 ,不携带等位基因C(IL 1RN C)的基因型 ,其患冠心病的相对风险度约是携带IL 1RN C基因型的 1.96倍 ;与心绞痛组比较 ,患心肌梗死的相对风险度约是 4.0 9倍。结论　IL 1RN第 2号外显子 +80 0 6T C位点基因多态性与冠心病的发生、发展及该疾病的严重程度密切相关 ,IL 1RN C在其中可能具有保护作用。     

Fifteen percent of myocardial infarctions and coronary revascularizations explained by family history unrelated to conventional risk factors. The Reykjavik Cohort Study.

Aims To examine the relationship between history of myocardial infarction in first-degree relatives and the risk of developing coronary heart disease (myocardial infarction or coronary revascularization).Methods and Results A total of 9328 males and 10062 females, randomly selected residents of the Reykjavik area, aged 33-81 years, were examined in the period from 1967 to 1996 in a prospective cohort study. Cardiovascular risk assessment was based on characteristics at baseline. Information on history of myocardial infarction in first-degree relatives was obtained from a health questionnaire. Mean follow-up was 18 and 19 years for men and women, respectively. During follow-up 2700 men and 1070 women developed coronary heart disease. Compared with subjects without a family history, the hazard ratio of coronary heart disease was 1.75 (95% confidence interval, CI, 1.59-1.92) for men and 1.83 (95% CI, 1.60-2.11) for women, with one or more first-degree relatives with myocardial infarction. The risk factor profile was significantly worse in individuals with a positive family history. After allowance for these risk factors, the hazard ratio was still highly significant, 1.66 (CI, 1.51-1.82) and 1.64 (CI, 1.43-1.89) for men and women, respectively. Family history of myocardial infarction was attributed to 15.1% of all cases of coronary heart disease in men and 16.6% in women, independent of other known risk factors.Conclusion Family history of myocardial infarction increases the risk of developing coronary heart disease in both men and women and is largely independent of other classic risk factors. Approximately 15% of all myocardial infarctions can be attributed to familial factors that have not been measured in the study or remain to be elucidated.     

Genetic polymorphism of platelet glycoprotein IIIa in patients with acute myocardial infarction and acute ischaemic stroke

BACKGROUND: It has recently been suggested that the Leu33Pro polymorphism of the platelet glycoprotein IIIa affects the risk of coronary thrombosis. Finland is genetically isolated and has an incidence of cardiovascular disease among the highest in the world. Interestingly, the prevalence of ischaemic heart disease also varies in different parts of the country, being highest in eastern Finland. METHOD: We studied the Leu33Pro polymorphism using polymerase chain reaction in 133 patients with coronary artery disease, 234 patients with cerebrovascular disease and 326 control subjects originating from two areas of Finland. RESULTS: The frequencies of the Pro33 allele in the patients with acute myocardial infarction and cerebrovascular attack were 13% and 14%, respectively, and did not differ from the controls (13%). Among patients with acute myocardial infarction from the Helsinki area, the family history of premature coronary artery disease was more often positive in carriers of the Pro33 allele than in non-carriers, but after adjustment for multiple comparisons the difference was no longer significant. CONCLUSIONS: We could not confirm the original observation that the Pro33 allele constitutes an independent risk factor for coronary artery disease. Further studies are needed to clarify whether co-occurrence of Pro33 and some unrecognized inherited factor pose an additional risk of vascular disease.     

早发冠心病心肌梗死型与非心肌梗死型危险因素差异分析

目的探讨早发冠心病中心肌梗死型与非心肌梗死型的危险因素差异。方法回顾性分析2004年1月至2009年12月在沈阳医学院附属奉天医院心血管内科住院并确诊的45岁及以下冠心病患者165例,分为急性心肌梗死(AMI)组和非AMI组。对两组患者的相关临床资料及危险因素进行统计分析。结果 AMI组吸烟史比例、男性比率、血浆纤维蛋白原及D-二聚体均高于非AMI组,差异有统计学意义(P<0.05),两组的血脂异常率、血小板计数(PLT)、血小板压积、凝血酶原时间(PT)、国际标准化比值(INR)和活化部分凝血活酶时间(APTT)的差异无统计学意义。结论吸烟、男性性别、血脂水平异常是早发冠心病重要危险因素;血浆纤维蛋白原水平增高对于预测早发冠心病心肌梗死可能具有一定的临床意义。     

Prognostic implications of asymptomatic ventricular arrhythmias: the Framingham Heart Study.

OBJECTIVE: To evaluate the prevalence and prognostic significance of asymptomatic complex or frequent ventricular premature beats detected during ambulatory electrocardiographic (ECG) monitoring. DESIGN: Cohort study with a follow-up period of 4 to 6 years. SETTING: Population-based. PARTICIPANTS: Surviving patients of the original Framingham Heart Study cohort and offspring of original cohort members (2727 men and 3306 women). MEASUREMENTS: One-hour ambulatory electrocardiography. RESULTS: The age-adjusted prevalence of complex or frequent arrhythmia (more than 30 ventricular premature complexes per hour or multiform premature complexes, ventricular couplets, ventricular tachycardia, or R-on-T ventricular premature complexes) was 12% (95% Cl, 11% to 13%) in the 2425 men without clinically evident coronary heart disease and 33% (Cl, 24% to 42%) in the 302 men with coronary heart disease. The corresponding values in women (3064 without disease and 242 with disease) were 12% (Cl, 11% to 13%) and 26% (Cl, 9% to 43%). After adjusting for age and traditional risk factors for coronary heart disease in a Cox proportional hazards model, men without coronary heart disease who had complex or frequent ventricular arrhythmias were at increased risk for both all-cause mortality (relative risk, 2.30; Cl, 1.65 to 3.20) and the occurrence of myocardial infarction or death from coronary heart disease (relative risk, 2.12; Cl, 1.33 to 3.38). In men with coronary heart disease and in women with and without coronary heart disease, complex or frequent arrhythmias were not associated with an increased risk for either outcome. CONCLUSIONS: In men who do not have clinically apparent coronary heart disease, the incidental detection of ventricular arrhythmias is associated with a twofold increase in the risk for all-cause mortality and myocardial infarction or death due to coronary heart disease. The preventive and therapeutic implications of these findings await further investigation.     

Comparison of risk factors in vasospastic angina without significant fixed coronary narrowing to significant fixed coronary narrowing and no vasospastic angina

To determine the importance of usual risk factors of coronary artery disease (CAD) in patients with coronary artery spasm, 40 patients with vasospastic angina (VA), normal or nearly normal coronary arteries and without previous myocardial infarction were compared with 2 control groups of 40 patients each, matched for age and sex: 1 group with CAD and 1 without heart disease. Ninety percent of patients with VA were cigarette smokers and 70% were heavy smokers (more than 20 cigarettes daily), compared with 53% and 33% in patients with CAD (p less than 0.001) and 30% and 15% in those without heart disease (p less than 0.001). Except for cigarette smoking, the risk factor profile of patients with VA appeared more like the profile of patients without heart disease than that of patients with CAD. The results suggest that cigarette smoking may play a role in CAD independent of atherosclerosis and possibly favoring coronary artery spasm.     

Abnormal coronary hemodynamics and myocardial energetics in patients with chronic heart failure caused by ischemic heart disease and dilated cardiomyopathy

Coronary sinus blood flow, transmyocardial oxygen extraction, myocardial oxygen consumption, and transmyocardial lactate extraction were determined, along with systemic hemodynamics, in 34 patients with chronic stable angina without heart failure (group 1), in 66 patients with heart failure associated with coronary artery disease (group 2), and in 28 patients with heart failure caused by dilated cardiomyopathy without coronary artery disease (group 3). Compared with group 1 patients, in patients with heart failure in groups 2 and 3, resting coronary sinus blood flow was 30% and 24% higher, respectively (p less than 0.05), myocardial oxygen consumption was 25% higher (p less than 0.01), and coronary sinus oxygen content was 33% lower (p less than 0.01). The rate-pressure product was not different between the three groups. In eight patients with heart failure (five in group 2 and three in group 3), myocardial lactate production was observed without angina. Thus in patients with chronic heart failure resulting from either chronic coronary artery disease or dilated cardiomyopathy, resting coronary blood flow and myocardial oxygen consumption tend to increase probably because of an increase in myocardial oxygen requirements. Silent myocardial ischemia may also occur in both the presence and absence of coronary artery disease in patients with chronic heart failure. The abnormal coronary hemodynamics and myocardial metabolic function may play a role in causing progressive deterioration in cardiac function in dilated cardiomyopathy.     

Effects of exercise training on mortality in patients with coronary heart disease

Endothelial dysfunction not only precedes the development of significant coronary artery stenosis, it has also been identified as a general phenomenon predicting future cardiovascular events in patients who are at risk. As regular physical activity as a part of a multifactorial intervention has been shown to affect symptoms beneficially, increase myocardial perfusion and--most importantly--reduce mortality in patients with coronary heart disease or myocardial infarction, this review will elucidate potential mechanisms responsible for the improvement in survival as a result of regular physical activity. The importance of exercise training-mediated regression of coronary stenosis, collateral formation, correction of endothelial dysfunction including the adaptation at the molecular level, as well as vasculogenesis will be discussed as possible underlying key players, and their potential contribution to the training-induced survival benefit in patients with coronary heart disease will be critically evaluated.     

Benefits of pravastatin on cardiovascular events and mortality in older patients with coronary heart disease are equal to or exceed those seen in younger patients: Results from the LIPID trial

BACKGROUND: The effect of cholesterol-lowering therapy on death from coronary heart disease in older patients with previous coronary heart disease and average cholesterol levels is uncertain. OBJECTIVE: To compare the relative and absolute effects of pravastatin on cardiovascular disease outcomes in patients with coronary heart disease who are 65 years of age or older with those in patients 31 to 64 years of age. DESIGN: Subgroup analysis of a randomized, placebo-controlled trial. SETTING: 87 centers in Australia and New Zealand. PATIENTS: 3514 patients 65 to 75 years of age, chosen from among 9014 patients with previous myocardial infarction or unstable angina and a baseline plasma cholesterol level of 4.0 to 7.0 mmol/L (155 to 271 mg/dL). INTERVENTION: Pravastatin, 40 mg/d, or placebo. MEASUREMENTS: Major cardiovascular disease events over 6 years. RESULTS: Older patients were at greater risk than younger patients (31 to 64 years of age) for death (20.6% vs. 9.8%), myocardial infarction (11.4% vs. 9.5%), unstable angina (26.7% vs. 23.2%), and stroke (6.7% vs. 3.1%) (all P < 0.001). Pravastatin reduced the risk for all cardiovascular disease events, and similar relative effects were observed in older and younger patients. In patients 65 to 75 years of age, pravastatin therapy reduced mortality by 21% (CI, 7% to 32%), death from coronary heart disease by 24% (CI, 7% to 38%), coronary heart disease death or nonfatal myocardial infarction by 22% (CI, 9% to 34%), myocardial infarction by 26% (CI, 9% to 40%), and stroke by 12% (CI, -15% to 32%). For every 1000 older patients treated over 6 years, pravastatin prevented 45 deaths, 33 myocardial infarctions, 32 unstable angina events, 34 coronary revascularization procedures, 13 strokes, or 133 major cardiovascular events, compared with 22 deaths and 107 major cardiovascular events per 1000 younger patients. Among older patients, the numbers needed to treat were 22 (CI, 17 to 36) to prevent one death from any cause, 35 (CI, 24 to 67) to prevent one death from coronary heart disease, and 21 (CI, 17 to 31) to prevent one coronary heart disease death or nonfatal myocardial infarction. CONCLUSIONS: In older patients with coronary heart disease and average or moderately elevated cholesterol levels, pravastatin therapy reduced the risk for all major cardiovascular events and all-cause mortality. Since older patients are at greater risk than younger patients for these events, the absolute benefit of treatment is significantly greater in older patients.     

Occupation and risk of nonfatal myocardial infarction.

BACKGROUND--While some analytic studies have suggested that individuals in occupations representing higher compared with lower socioeconomic status have a decreased risk of coronary heart disease, it is unclear whether occupation itself has an etiologic role in the development of coronary heart disease or whether differences in as yet uncontrolled coronary risk factors may account for these differences in risk. METHODS--White-collar vs blue-collar occupation and risk of coronary heart disease was evaluated among 230 male patients hospitalized for a first myocardial infarction and 222 control subjects of the same age, sex, and neighborhood of residence. Information on coronary risk factors was obtained from home interviews, and blood specimens were drawn to test lipid and lipoprotein levels. Usual occupation was dichotomized into white-collar and blue-collar occupation according to the Edwards' classification. RESULTS--The relative risk of myocardial infarction of white-collar compared with blue-collar workers was 0.74 (95% confidence interval, 0.46 to 1.19) after controlling for age, cigarette smoking, family history of premature myocardial infarction, history of treatment for high blood pressure, body mass index, history of diabetes, alcohol consumption, type A personality, leisure-time physical activity, total calories, and percentage of calories consumed as saturated fat. However, there was no residual association after control for high-density lipoprotein cholesterol yielding a relative risk of 0.98 (95% confidence interval, 0.59 to 1.63). CONCLUSIONS--These results suggest that white-collar occupation per se does not appear to protect from coronary heart disease. Any apparent protective effect on myocardial infarction that has been previously observed in white-collar compared with blue-collar workers may be attributable to differences in high-density lipoprotein cholesterol levels.