白细胞介素-23在炎症性肠病的表达升高并诱导促炎细胞因子分泌

目的 通过分析白细胞介素(IL)-23p19及其受体(IL-23R)在炎症性肠病(IBD)患者中的表达,研究IL-23对IBD患者外周血T细胞激活和效应应答的影响,探讨其在疾病发生过程中的免疫病理作用.方法 收集12例克罗恩病(CD)患者、25例溃疡性结肠炎(UC)患者和20名健康者外周血和肠黏膜组织活检标本,使用免疫组化染色和逆转录(RT)-PCR分析IL-23p19表达,分离外周血单个核细胞(PBMC)和肠黏膜固有层内单个核细胞(LPMC),利用流式细胞仪检测IL-23R在CD4+、CD8+T细胞和自然杀伤(NK)细胞表面表达.体外培养PBMC,使用IL-23和抗CD3单抗体外刺激,使用酶联免疫吸附试验检测肿瘤坏死因子(TNF)-α、干扰素(IFN)-γ和白细胞介素(IL)-2分泌.结果 IBD患者炎症肠黏膜组织内IL-23p19蛋白和mRNA表达水平比健康对照者显著升高(P<0.05).IL-23R在IBD患者外周血和肠黏膜固有层组织内CD4+、CD8+T细胞和NK细胞表达水平也比健康者显著升高(P<0.05).体外培养PBMC,使用IL-23刺激,发现IL-23可显著诱导IBD患者,尤其是CD患者PBMC激活,分泌高水平TNF-α、IFN-γ和IL-2(P<0.05).结论 IL-23及其受体在IBD患者炎症肠黏膜组织中表达升高,IL-23可诱导IBD患者淋巴细胞分泌高水平的炎性介质,提示IL-23参与了肠黏膜炎症损伤,阻断IL-23生物学效应可能治疗IBD.     

IL-27在炎症性肠病炎症肠黏膜中的表达及意义

目的:检测克罗恩病(CD)和溃疡性结肠炎(UC)肠黏膜组织中IL-27 p28 mRNATL其蛋白、IL-27受体mRNA的表达,探讨其在CD和UC中的发病意义.方法:应用反转录-聚合酶链反应(RT-PCR)和蛋白质免疫印迹(Western blot)方法检测炎症性肠病患者炎症肠黏膜组织中IL-27 p28基因及蛋白、IL-27受体基因的表达,并与健康者作对照.结果:IL-27 p28 mRNA在CD患者中的阳性率和灰度分析表达较UC患者明显增高(X2=6.64,P<0.05;t=11.01,P<0.01),IL-27受体阳性率和灰度分析在CD患者较UC患者和健康对照者明显增高(阳性率:X2=10.91,P<0.016,X2=18.84,P<0.016).IL-27蛋白阳性率和灰度分析在CD患者中表达明显高于UC患者(X2=5.24,P<0.05;t=3.37,P<0.05),并且IL-27mRNA的表达与蛋白质表达密切相关.结论:IL-27 p28及其受体的上调,可能有助于CD患者炎症发展过程.     

Saliva Interleukin-6 in patients with inflammatory bowel disease

Objective. The inflammatory bowel diseases (IBD), Crohn's disease (CD) and ulcerative colitis (UC) are chronic inflammatory conditions that affect the gastrointestinal tract. In regulation of this inflammatory process, Interleukin-6 (IL-6) has a major role. Overproduction of IL-6 by immunocompetent cells contributes to development of the inflammatory condition. Elevated levels of IL-6 in saliva could be expected, because the saliva-producing cells are part of the digestive system. Material and methods. IL-6 concentrations in saliva and plasma were studied in patients with CD (n=15), UC (n=7) and reference persons (RP) (n=19) by use of an ELISA method. Results. A significant difference in saliva IL-6 concentration between CD patients (median 16.9 ng/L; p<0.05) and RP (median 6.3 ng/L) was found. A significant difference in plasma IL-6 concentration between CD (median 10.3 ng/L; p<0.001) or UC (median 7.8 ng/L; p<0.001) and RP (median 0.8 ng/L) was observed. In patients with CD, plasma IL-6 correlated significantly with C-reactive protein (CRP) as well as albumin. In patients with UC, saliva IL-6 and plasma IL-6 correlated significantly with AI (activity index) scores as well as albumin. In patients with UC, a significant correlation between the saliva and plasma IL-6 concentrations was found. Conclusions. IL-6 was found in saliva in patients with IBD, documenting the general involvement of the gastrointestinal tract extending to the mouth cavity, and measuring IL-6 may be an additional method for evaluating and monitoring the disease activity.     

Roles of galectins in inflammatory bowel disease Aikira Hokama,Emiko Mizoguchi,Atsushi Mizoguchi

Protein/carbohydrate interactions through specific protein families termed lectin control essential biological processes.Galectins,a family of animal lectins defined by shared amino acid sequence with affinity for β-galactosides,appear to be functionally polyvalent in a wide range of biological activity.Recent studies have identified immunoregulatory roles of galectins in intestinal inflammatory disorders.Galectin-1 and galectin-2 contribute to the suppression of intestinal inflammation by the induction of apoptosis of activated T cells,whereas galectin-4 is involved in the exacerbation of this inflammation by specifically stimulating intesUnal CD4 T cells to produce IL-6.We review how different members of the galectins provide inhibitory or stimulatory signals to control intestinal immune response under intestinal infiammation.(C)2008 The WJG Press.All rights reserved.     

白介素-10与炎症性肠病

炎症性肠病(inflammatory bowel disease,IBD)是一种慢性、复发性的肠道炎症疾病,其明确病因目前仍不清楚.肠道免疫功能异常导致过量炎症因子释放损伤肠道黏膜在IBD发病中起着关键作用,应用免疫抑制剂减少炎症因子的释放也被应用于IBD的治疗.近年来利用细胞因子调节机体免疫功能以治疗IBD的研究日渐...     

IL-17基因多态性与中国汉族人群炎症性肠病的关系

目的:研究IL-17A和IL-17F的5个多态性位点与中国汉族人炎症性肠病之间的关系.方法:采用病例-对照研究方法,收集确诊的溃疡性结肠炎(ulcerative colitis,UC)和克罗恩病(Crohn’s disease,CD)患者共350例(UC270例;CD80例),健康对照组268例,收集外周血标本2mL,提取DNA,运用LDR(ligasedetection reaction allelic)技术进行多态性检测.采用SPSS17.0软件进行数据分析.结果:CD患者中IL-17F(rs763780,7488T/C)突变等位基因C的频率明显高于对照组(13.8%vs8.4%,P=0.044,OR=1.74,95%CI1.01-2.99).在亚型分析中,rs763780基因多态性与CD病变范围有关,突变等位基因C在CD回结肠型患者中的频率明显高于对照组(P=0.02).IL-17A(rs2275913,G-197A)与UC患者疾病的严重程度有弱相关性,含有突变基因A的患者倾向于临床轻型.IL-17F(rs763780,7488T/C)多态性与U C患者发病年龄之间有弱相关性,T/C基因型患者趋向于年轻型(P=0.046).结论:IL-17F rs763780基因多态性与CD易感性之间有弱相关性,在亚组分析中发现rs763780与CD的病变范围和UC的发病年龄有关.IL-17A rs2275913基因多态性与UC疾病严重程度呈负相关.     

MicroRNAs与炎症性肠病

炎症性肠病(IBD)的发病机制与免疫、炎症、损伤、遗传等因素密切相关。MicroRNAs是一类小的非编码RNA,其通过与靶基因3’UTR区结合,负向调控基因表达,在炎症性肠病的发病机制中发挥重要的作用。     

Special issues in pediatric inflammatory bowel disease

The incidence of pediatric inflammatory bowel disease （IBD） is rising and recent advances in diagnostics and therapeutics have improved the care provided to these children. There are distinguishing features worth noting between early onset and adult onset IBD. Physical and psychosocial development remains a critical target for the comprehensive management of pediatric IBD. Children are not just little adults and consideration must be given to the stages of development and how these stages impact disease presentation and management. The final stage will be the transition from pediatric care to that of adult oriented care and special consideration must be given to make this a successful process. This review highlights special considerations in the management of the child with IBD.     

Th17细胞在炎症性肠病发病机制作用的研究进展

炎症性肠病的病因和发病机制尚未完全明确。最近的研究表明,Th17细胞及与其相关的细胞因子、Th细胞亚群所导致的炎症过程在炎症性肠病的发生发展中起重要作用。本文就Th17的分化调控机制及Th17与其相关的细胞因子、Th细胞亚群在炎症性肠病的发病机制中的作用作一概述。     

IL-17在炎性肠病中的表达及其与LPS协同诱导肠上皮细胞表达IL-8的作用机制

目的:探讨IL-17细胞因子在TNBS诱导的炎性肠病动物模型中的表达变化,明确IL-17和脂多糖(LPS)在诱导HT-29肠上皮细胞IL-8表达中的协同作用及细胞内信号机制.方法:探讨IL-17及其受体在TNBS炎性肠病模型中的表达变化,利用细胞培养、FASC、Real-time PCR、酶联免疫吸附(ELISA)、Western blot等技术,观察IL-17及不同剂量LPS干预人肠上皮细胞(HT-29细胞)后细胞因子IL-8在蛋白水平的表达,以及IL-17受体(IL-17Ra)在mRNA水平的表达变化及引起上述效应的细胞内信号传导机制.结果:TNBS诱导的炎性肠病动物模型中IL-17以及IL-17Ra显著升高(P<0.03);炎症介质IL-17能与一定浓度范围内的LPS协同促进IL-8的表达(2187.61±132.42vs2634.27±134.63,P=0.01),增强NF-κB信号通路的活化,促进炎症反应.但随着LPS剂量升高,LPS本身诱导IL-8表达的活性降低,且与IL-17的协同作用消失(1841.43±50.38vs1685.67±71.47,P=0.03).结论:IL-17与低浓度的LPS可协同促进HT-29细胞炎症介质的表达,但与高浓度LPS联合时,两者无协同效应.     

肠易激综合征与炎症性肠病

近年发现,炎症性肠病(IBD)患者发病早期或缓解期时常表现为肠易激综合征(IBs)症状,且IBD与IBS的临床表现具有一定的相似性。因而IBS与IBD的相关性受到广泛的重视。此文就IBS与IBD的发病机制及临床相关性予以阐述,以期为临床个体化治疗提供借鉴。     

State-of-the-art of irritable bowel syndrome and inflammatory bowel disease research in 2008

Irritable bowel syndrome （IBS） and inflammatory bowel disease （IBD） are two of the leading causes of chronic intestinal conditions in the world. This issue of World Journal of Gastroenterology （ WJG） presents a series of papers from world experts who discuss the current knowledge and opinions on these important conditions. Although great strides have been made in the diagnosis, treatment and pathology of IBS and IBD; much has yet to be explained. The etiologies and risk factors of these multifactorial conditions remain elusive. Specific diagnostic biomarkers need to be developed and safer treatments developed. The burden of IBS and IBD on the healthcare system is felt with repeated medical care visits and high costs. IBS and IBD patients can account for 30%-50% of office visits at gastroenterology services/clinics. Over one million people have IBD in the United States, with 30000 new cases being diagnosed every year. One-quarter million people in the UK are afflicted with IBD. The cost of medical care in the United States for IBD is estimated to be $1.8 billion/year.     

Extraintestinal manifestations in inflammatory bowel disease

Inflammatory bowel diseases (IBD) can be really considered to be systemic diseases since they are often associated with extraintestinal manifestations, complications, and other autoimmune disorders. Indeed, physicians who care for patients with ulcerative colitis and Crohn's disease, the two major forms of IBD, face a new clinical challenge every day, worsened by the very frequent rate of extraintestinal complications. The goal of this review is to provide an overview and an update on the extraintestinal complications occurring in IBD. Indeed, this paper highlights how virtually almost every organ system can be involved, principally eyes, skin, joints, kidneys, liver and biliary tracts, and vasculature (or vascular system) are the most common sites of systemic IBD and their involvement is dependent on different mechanisms.     

基因多态性与炎症性肠病发病的关系

炎症性肠病(IBD)发病机制复杂,近年来多项研究显示,相关基因的多态性在IBD发病中起重要作用,本文对其中主要基因与IBD的关系作一综述.     

Pharmacogenetics in inflammatory bowel disease

Pharmacogenetics is the study of the association between variability in drug response and (or) drug toxicity and polymorphisms in genes. The goal of this field of science is to adapt drugs to a patient's specific genetic background and therefore make them more efficacious and safe. In this article we describe the variants in genes that influence either the efficacy or toxicity of common drugs used in the treatment of inflammatory bowel diseases (IBD), ulcerative colitis (UC), and Crohn's disease (CD) including sulfasalazine and mesalazine, azathioprine (AZA) and 6-mercaptopurine (6-MP), methotrexate (MIX), glucocorticosteroids (CSs) and infliximab. Furthermore, difficulties with pharmacogenetic studies in general and more specifically in IBD are described. Although pharmacogenetics is a promising field that already contributed to a better understanding of some of the underlying mechanisms of action of drugs used in IBD, the only discovery translated until now into daily practice is the relation between thiopurine S-methyltransferase (TPMT) gene polymorphisms and hematological toxicity of thiopurine treatment. In the future it is necessary to organize studies in well characterized patient cohorts who have been uniformly treated and systematically evaluated in order to quantitate drug response more objectively. An effort should be made to collect genomic DNA from all patients enrolled in clinical drug trials after appropriate informed consent for pharmacogenetic studies.     

T淋巴细胞亚群在炎症性肠病中作用的研究

炎症性肠病(inflammatory bowel disease,IBD)主要包括溃疡性结肠炎(ulcerative colitis,UC)和克罗恩病(Crohn's disease,CD),是一种反复发作的慢性炎症性肠道疾病,通常认为IBD的发生、发展与自身免疫系统异常关系密切.胃肠道需要在耐受内容物及对病原体的免疫...     

白细胞介素-25在炎症性肠病患者中的表达及临床意义

目的 通过检测白细胞介素(IL)-25在炎症性肠病(IBD)患者肠黏膜及血清中的表达水平,探讨其在IBD发病过程中的作用及意义.方法 收集12例溃疡性结肠炎(UC)患者、16例克罗恩病(CD)患者及13例对照者的内镜肠黏膜活检标本,采用荧光定量PCR技术检测肠黏膜内IL-25 mRNA的表达情况,免疫组化技术分析IL-25在肠黏膜中的原位表达;同期收集20例UC、24例CD患者及20名健康对照者血清标本,采用酶联免疫吸附测定(ELISA)检测血清中IL-25水平.结果 与健康对照组相比,UC及CD患者肠黏膜组织内IL-25 mRNA表达显著降低(P＜0.05),UC及CD组间的表达量差异无统计学意义(P＞0.05).免疫组化分析显示IL-25阳性细胞在正常肠黏膜固有层内有较多表达,同时黏膜内的肠上皮细胞也存在IL-25低表达,UC及CD患者肠黏膜IL-25蛋白表达量显著降低(P＜0.05),UC及CD组间的表达量差异无统计学意义(P＞0.05).ELISA显示UC及CD患者血清中IL-25表达量显著低于健康对照组(P＜0.05).结论 IL-25在IBD患者肠黏膜及血清中表达显著降低,提示IL-25表达缺陷与IBD的发生发展密切相关,IL-25有可能成为IBD治疗的新靶点.     

微生态失衡与炎症性肠病

炎症性肠病(IBD)包括克罗恩病(CD)和溃疡性结肠炎(UC),其病因和发病机制目前尚不清楚。研究发现,肠道微生态失衡即肠道致病菌和益生菌之间的平衡失调,在IBD的发生和发展中发挥重要作用。此文就微生态失衡在IBD发病中的作用作一综述。