白细胞介素11在哺乳动物生殖过程中的作用

白细胞介素 1 1 ( IL-1 1 )是以 gp1 3 0为信号转导因子的细胞因子。IL-1 1受体 ( IL-1 1 R)有 IL-1 1 Rα和 IL-1 1 Rβ两种同工型。 IL-1 1与靶细胞表面的特异性受体 IL-1 1 R结合后 ,通过活化细胞内的 JAK-STAT信号传导途径 ,影响基因表达 ,实现其生理作用。 IL -1 1及其受体参与哺乳动物特别是雌性动物生殖过程中许多环节的调节 ,如在蜕膜化、胚胎着床、绒毛膜胎盘形成等过程中起着关键性调节作用     

子宫内膜异位症患者血清及腹腔液细胞因子白细胞介素6、白细胞介素8的检测

子宫内膜异位症(EM)近年来发病率呈上升趋势,已成为育龄妇女的常见病和多发病.研究发现,EM的发病与细胞因子存在着密切的关系[1].为了探讨细胞因子在EM发病中的作用,观察了白细胞介素(IL)-6和IL-8两种细胞因子在EM患者血清及腹腔液中的变化.     

子宫内膜异位病患者血清及腹腔液细胞因子白细胞介素6、白细胞介素8的检测

子宫内膜异位症 ( EM)近年来发病率呈上升趋势 ,已成为育龄妇女的常见病和多发病。研究发现 ,EM的发病与细胞因子存在着密切的关系 [1]。为了探讨细胞因子在 EM发病中的作用 ,观察了白细胞介素 ( IL) -6和 IL-8两种细胞因子在 EM患者血清及腹腔液中的变化。一、材料和方法1 .研究对象 :1 999年 1 1月～ 2 0 0 0年 6月就诊于山西医科大学第一、二、三附属医院 ,行腹腔镜检查和开腹手术的不育患者共 72例 ,年龄 2 0～ 40岁。根据术后诊断分为 4组 :EM患者 43例 ,平均年龄 3 5.4岁 ,根据 1 985年美国生育协会 ( AFS)修正的标准分期 [2 ]…     

白细胞介素-8与肾脏疾病

白细胞介素-8是一种来源广泛、生物功能多样的趋化因子，通过对中性粒细胞等白细胞的趋化活化参与了多种肾脏疾病的发生、发展。它在体内的生物信号网络中占有重要的地位，生理、病理情况下的多种因素均可通过调控IL-8的合成、分泌而发挥功能。     

白细胞介素-8与肾脏疾病

白细胞介素 8是一种来源广泛、生物功能多样的趋化因子 ,通过对中性粒细胞等白细胞的趋化活化参与了多种肾脏疾病的发生、发展。它在体内的生物信号网络中占有重要的地位 ,生理、病理情况下的多种因素均可通过调控IL 8的合成、分泌而发挥功能     

白细胞介素-1β激活核转录因子-kB介导A549细胞分泌白细胞介素-8的研究

目的研究白细胞介索-1β（IL-1β）对肺Ⅱ型上皮A549细胞分泌白细胞介素-8（IL-8）的诱导作用，探讨相关的细胞内信号通道的激活和传导的机理。方法以1ng／ml终浓度的IL-1β干预经核转录因子-KB（NF-KB）的IKK2复合物抑制物（AS602868）预处理的A549细胞，Western blot检测IL-1β干预后细胞内磷酸化IKBa（p-IKBu）和IkBα蛋白的表达水平；激光扫描共焦显微镜（LSCM）检测NF-KB的p65和p50蛋白的核转移过程；ELISA检测NF-KB的p65和p50蛋白与DNA结合活性及IL-8蛋白的释放。结果IL-1β干预后细胞内p-IKBa蛋白明显升高，IKBd蛋白明显下降；LSCM扫描显示p65和p50蛋白从胞浆向胞核转移，同时p65和p50与DNA结合活性明显升高（P〈0．01）；IL-8的蛋白表达水平明显升高（P〈0．01）。细胞经AS602868的预处理，阻断了细胞内p-IxBa蛋白升高和IkBa蛋白降解；减少了p65和p50蛋白的核转移和与DNA结合活性（P〈0．01）；降低了IL-8蛋白的表达水平（P〈O．01）。结论IL-1β通过激活NF-KB介导了A549细胞分泌IL-8，结果提示可能通过抑制NF-kB信号通道的方法，减轻呼吸机相关肺损伤（VALI）的生物性损伤。     

白细胞介素-8及其与肾脏疾病的关系

白细胞介素-8(Interleukin-8,IL-8)是20世纪80年代后期发现并命名的一种新的细胞因子.IL-8由多种细胞产生,包括外周血淋巴细胞、单核细胞、中性粒细胞等,近来发现肾脏系膜细胞、内皮细胞及肾小管上皮细胞也可产生[1,2].IL-8对T淋巴细胞、中性粒细胞、嗜碱性粒细胞有趋化作用,是趋化因子中活性最强的一种[3],IL-8对T细胞的定位分布、淋巴细胞再循环、炎症或白细胞积聚有重大意义.IL-8参与多种炎症疾患的发病过程[3～6].IL-8作为一种炎症趋化因子,其在肾脏疾病中的作用开始引起重视.     

食管癌易感性与白细胞介素-8基因多态性的关系

目的 探讨白细胞介素(IL)-8多态性与食管癌发生危险因素的关系.方法 采用以医院为基础的病例对照研究方法,以高分辨率熔解曲线(HRM)小片段扩增子法分析351例食管癌和384例非肿瘤对照IL-8基因多态性,计算各种基因型的食管癌发生风险及其95%可信区间.结果 IL-8-251(A/T)多态3种基因型TT、AT、AA在食管癌组和非肿瘤对照组的频率分别为39.9%(IT)、54.7%(AT)、5.4%(AA)和43.8%(TT)、45.3%(AT)、10.9%(AA),与携带IL-8-251TT基因型的个体比较,IL-8-251 AA等位基因型可以减少46%食管癌的发病风险.结论 IL-8-25l(A/T)基因多态性AA基因型可能是食管癌发生的保护性因素.

Abstract：

Objective To investigate the relationship between interleukin-8 (IL-8) polymorphism and the susceptibility to esophageal cancer in a Chinese Han population. Methods Genotypes were determined by the high resolution melting (HRM) method in 351 esophageal cancer cases and 384 controls without cancers. Results The IL-8 genotype frequency was 39. 9% ( TF), 54. 7% (AT), 5.4% (AA)in the esophageal cancer group, and 43.8% (TT), 45. 3% (AT), 10. 9% (AA) in the control group respectively. Logistic regression analyses revealed that the risk associated with IL-8 variant genotype was 0. 54 (95% CI =0. 30-0. 98) for IL-8 AA compared with its wild-type homozygote. Conclusion IL-8 AA polymorphism may serve as a protective biomarker of esophageal cancer susceptibility.     

白细胞介素8在人乳腺癌细胞侵袭和增殖中的作用

目的探讨白细胞介素8（IL－8）在乳腺癌细胞侵袭和增殖中的作用。方法运用细胞因子抗体芯片技术分析11株人类乳腺癌细胞的细胞因子表达谱,研究细胞因子在乳腺癌进展中的作用机制。结果细胞因子表达谱显示IL－8的表达水平与乳腺癌细胞雌激素受体状态,转移能力和波形丝蛋白的状态均相关,与人类乳腺癌细胞的侵袭直接正相关。IL－8抗体可以特异性地阻断IL－8介导的细胞侵袭作用,但对乳腺癌细胞增殖无明显作用。结论IL－8可能是乳腺癌进展和细胞侵袭中的关键因子,在乳腺癌细胞侵袭中起重要作用。     

Interleukin-6 and interleukin-8 in the urine of children with acute pyelonephritis

Interleukin-6 (IL-6) and interleukin-8 (IL-8) are important mediators of the inflammatory response in serious bacterial infections. We studied the levels of these two cytokines (standardised for urinary creatinine) in the urine of infants and children during and 6 weeks after acute pyelonephritis and in non-renal febrile controls and healthy children without apparent infection. IL-6 was detected in the urine of 52% of children with pyelonephritis compared with 15% of other children (P<0.001). The median urinary IL-6 level in acute pyelonephritis was 4 pg/mol compared with undetectable levels in the control group (P<0.001). IL-8 was detected in 98% of children with pyelonephritis and 42% of other children (P<0.001). The median concentration of IL-8 was 188 pg/mol in pyelonephritis; it was undetectable in controls (P<0.001). IL-8 levels were higher in children less than 1 year of age (P<0.001).     

Urinary interleukin-6 and interleukin-8 in children with urinary tract infection

Urinary interleukin-6 (UIL-6) and urinary interleukin-8 (UIL-8) concentrations were measured by immunoassay in 39 and 34 patients respectively, hospitalized with febrile urinary tract infection (UTI), and in 37 and 32 age-, race- and sex-matched febrile control children respectively, with negative urine cultures. UIL-6 and UIL-8 concentrations, measured in picograms per milliliter and corrected for creatinine, were compared with clinical and laboratory indicators of inflammation and bacterial virulence factors of Escherichia coli. Median UIL-6 concentrations at the time of admission were 397 pg/ml (range 0–65,789 pg/ml) in the 37 patients compared to 0 pg/ml (range 0–473.8 pg/ml) in the 37 controls (P<0.0001). Median UIL-8 concentrations at the time of admission were 5809 pg/ml (range 0–347,368 pg/ml) in the 32 patients compared to 0 pg/ml (range 0–2231 pg/ml) in the 32 controls (P<0.0001). UIL-6 and UIL-8 concentrations were lower (P<0.0001 for UIL-6 and P=0.0005 for UIL-8) in follow-up urine samples from UTI patients, obtained 48 h after the initiation of antibiotic therapy. UIL-6 and UIL-8 concentrations were statistically significantly correlated with urine white blood cells (WBC). UIL-8 concentrations were elevated in patients with E. coli organisms producing hemolysin. UIL-6 and UIL-8 are elevated in children with febrile UTI and decrease in response to antibiotic therapy. Magnitude of UIL-8 response is associated with hemolysin production, a bacterial virulence factor of E. coli. UIL-6 and UIL-8 concentrations are statistically correlated with urine WBC. UIL-6 and UIL-8 may be mediators of inflammation in children with febrile UTI. Received: 30 June 1999 / Revised: 29 June 2000 / Accepted: 5 July 2000     

Osteoblasts derived from osteophytes produce interleukin-6, interleukin-8, and matrix metalloproteinase-13 in osteoarthritis

To clarify the significance of the osteophytes that appear during the progression of osteoarthritis (OA), we investigated the expression of inflammatory cytokines and proteases in osteoblasts from osteophytes. We also examined the influence of mechanical stress loading on osteoblasts on the expression of inflammatory cytokines and proteases. Osteoblasts were isolated from osteophytes in 19 patients diagnosed with knee OA and from subchondral bone in 4 patients diagnosed with femoral neck fracture. Messenger RNA expression and protein production of inflammatory cytokines and proteases were analyzed using real-time RT-PCR and ELISA, respectively. To examine the effects of mechanical loading, continuous hydrostatic pressure was applied to the osteoblasts. We determined the mRNA expression and protein production of IL-6, IL-8, and MMP-13, which are involved in the progression of OA, were increased in the osteophytes. Additionally, when OA pathological conditions were simulated by applying a nonphysiological mechanical stress load, the gene expression of IL-6 and IL-8 increased. Our results suggested that nonphysiological mechanical stress may induce the expression of biological factors in the osteophytes and is involved in OA progression. By controlling the expression of these genes in the osteophytes, the progression of cartilage degeneration in OA may be reduced, suggesting a new treatment strategy for OA.     

Role of interleukin-8 in onset of the immune response in intravesical BCG therapy for superficial bladder cancer

In intravesical therapy for superficial bladder carcinoma urothelial cells may, through the production of cytokines, contribute to the bacillus Calmette-Guérin (BCG)-induced local immunological reaction and associated antitumor efficacy. The aim of this study was to investigate such a role for the neutrophil-attracting cytokine interleukin-8 (IL-8). The appearance of IL-8 in patients' urine after BCG therapy was compared with BCG-induced IL-6 and IL-2 and the stability of IL-8 in urine was tested. Compared to IL-6 and IL-2, a rapid induction of IL-8 was observed, occurring after the first BCG instillation. Urinary IL-8 was highly stable, even after 24 h incubation at 37°C. The IL-8 concentration after the first instillation seemed to be associated with subsequent development of an immune response. Consequently, IL-8 seems an attractive candidate for investigation of its prognostic value for a clinical response to BCG therapy.     

Systemic liberation of interleukin-8 in the perioperative phase of liver transplantation

Serum levels of interleukin-8 (IL-8) were investigated in the perioperative phase of liver transplantation (LTx) in order to help determine whether this cytokine might serve as a parameter for preservation injury. In a study of 45 patients undergoing LTx, systemic IL-8 was estimated at the end of the anhepatic phase, at 30, 60, and 120 min after reperfusion of the graft, and 24 h and 7 days after LTx. A maximum mean concentration of 665 ± 135 pg/ml was seen 60 min after LTx. The minimum was found on the 1st postoperative day (POD 1): 328 ± 33 pg/ml. Significant changes were found between 60 min and PODs 1 and 7, as well as between 120 min and POD 1. Differences in cold ischemia time were not found to be significant. We conclude that monitoring of systemic IL-8 levels is not useful in the development of new liver preservation concepts. Received: 12 September 1996 Received after revision: 27 February 1997 Accepted: 3 March 1997     

白细胞介素-8的表达与乳腺癌预后的关系

目的探讨白细胞介素-8（IL-8）在乳腺癌组织中的表达及与预后的关系。方法应用组织芯片技术,通过免疫组化法,检测IL-8在113例乳腺癌、19例乳腺良性肿瘤和20例正常乳腺组织中的表达,分析其与乳腺癌临床病理特征及预后的关系。结果IL-8在乳腺癌组织中的阳性表达率为27．4％,明显高于在乳腺良性肿瘤（5．3％）及正常乳腺组织（0）中的表达（X^2=9．936,P=0．002）。IL-8表达与乳腺癌组织学类型（X^2=4．202,P=0．040）和淋巴结转移（X^2=7．716,P=0．021）有关;IL-8阳性率与ER、PR表达呈负相关（X^2=5．885,P=0．015和X^2=4．504,P=0．034）,与C-erbB-2表达呈正相关（X^2=9．276,P=0．002）。IL-8表达阳性组与阴性组的5年无瘤生存率分别为63．89％和87．08％,差异有统计学意义（QPH=4．67,P=0．031）。结论IL-8阳性表达提示乳腺癌预后不良。IL-8可作为评价乳腺癌预后的新的生物学指标,为乳腺癌综合治疗提供依据。     

胃癌组织中白细胞介素-8基因启动子甲基化及其mRNA表达的研究

目的 观察胃癌患者癌组织及与其配对的正常胃黏膜组织中白细胞介素-8(IL-8)基因启动子甲基化及其mRNA表达,探讨IL-8基因甲基化与胃癌的关系.方法 收集经病理确诊并行外科手术切除的胃癌组织及配对的正常胃黏膜组织各52例,用实时荧光定量聚合酶链反应(FQ-PCR)分别检测癌组织及正常组织中IL-8基因mRNA表达;用甲基化特异性PCR(MSP)检测上述两种组织中IL-8基因甲基化状态.结果 胃癌组织中IL-8基因mRNA的表达量是正常组织中的1.94倍(P＜0.01).胃癌组织中IL-8基因甲基化率为32.7％,而正常组织中的甲基化率为73.1％(P＜0.01);胃癌组织中IL-8基因mRNA表达及启动子的去甲基化与性别、年龄、肿瘤大小无明显相关(P＞0.05),而与肿瘤的分化程度、Borrmann分型、浸润程度及有无淋巴结转移均具有明显相关(P＜0.05);去甲基化的胃癌组织中IL-8 mRNA表达是甲基化胃癌组织的2.13倍(P ＜0.001).结论 IL-8基因mRNA在胃癌组织中过表达;胃癌组织中IL-8基因启动子区呈低甲基化状态;IL-8基因启动子区去甲基化促进了其在胃癌组织中高表达.     

丙泊酚对大鼠肾缺血-再灌注期血清白细胞介素-8的影响

目的观察丙泊酚对大鼠肾缺血-再灌注期血清白细胞介素-8(IL-8)的合成和释放的影响,并探讨其肾保护机制。方法选用12~14周雄性大鼠75只,随机分为三组,每组25只,以无创动脉夹夹闭双侧肾蒂60min制备急性肾缺血-再灌注模型。A组为肾缺血-再灌注组,B组为丙泊酚处理组,C组为假手术组。各组设立五个时间观察点:缺血前10min(T0),缺血60min(T1),再灌注1h(T2)、3h(T3)、6h(T4),每个时间点5只大鼠。C组:肾脏缺血60min,缺血前5min从股静脉注射丙泊酚20mg/kg,继之经微量泵持续输入丙泊酚(0·5mg/ml)50mg·kg-1·h-1,持续60min;A、B组以等容生理盐水取代丙泊酚,但A组不夹闭双侧肾蒂,术中保持大鼠呼吸、循环稳定。各组大鼠存活至预定时间后再次麻醉取标本,测定血浆丙二醛(MDA)、超氧化物歧化酶(SOD)、血清IL-8,同时用光学显微镜观察肾组织形态学改变及肾小管损伤情况。结果血浆MDA在C组T1~T4时无明显变化,同A组相似,较B组相应时点显著降低,而B组T1~T4时较T0时及A组各时点显著升高;SOD则呈相反变化;C组T1~T3时血清IL-8无明显变化,仅在T4时较T0时和A组有显著升高,而B组在T1~T4时分别增加1·73、2·50、2·76、2·89倍,同C组和A组相比有显著性差异;光镜下观察发现B组肾小管上皮细胞变性、坏死,细胞脱落,肾小管管腔变窄,肾间质水肿、充血伴炎性细胞浸润明显;而C组以肾小管肿涨为主,个别呈坏死样改变,肾间质水肿、充血、炎性细胞浸润不明显。结论丙泊酚除了有抗氧作用外,还能有效地抑制血清IL-8合成和释放,这可能是丙泊酚减轻肾缺血-再灌注损伤的机制之一。