Graves病患者甲状腺组织内IL-6及gp130表达增强

对8例Graves病(GD)甲状腺组织内白细胞介素6(IL-6)及其受体(gp80、gp130)表达进行研究,发现GD组甲状腺组织内IL-6mRNA、gp130mRNA表达增高;GD中甲状腺滤泡细胞和淋巴细胞胞浆IL-6表达水平显著升高.提示GD患者甲状腺内IL-6/gp130信号通路的激活可能参与GD的发病.     

狼疮肾炎患者外周血单个核细胞内白细胞介素—6gp80与gp130 …

目的 了解狼疮肾炎（ＬＮ）患者外周血单个核细胞（ＰＢＭＣｓ）白细胞介素－６（ＩＬ－６）与ＩＬ－６受体（ｇｐ８０与ｇｐ１３０）的ｍＲＮＡ表达情况，并分析它们之间及其与自身抗体的关系。方法 采用逆转录聚合酶链反应（ＲＴ－ＰＣＲ）方法检测１８例活动期ＬＮ患者、１６例非活动期ＬＮ患者和１０名正常人ＰＢＭＣｓ内ＩＬ－６、ｇｐ８０与ｇｐ１３０的ｍＲＮＡ表达水平。结果 ①活动期ＬＮ患者、非活动期ＬＮ患者及正常人     

骨质疏松大鼠骨髓白细胞介素6受体亚单位gp80和gp130基因的表达

以竞争性RT-PCR研究骨质疏松模型大鼠骨髓白细胞介素6受体亚单位gp80和gpl30基因的表达。结果表明这些骨质疏松大鼠的gp80和gp130 mRNA基因表达增加，该变化可能为雌激素丢失所致骨质疏忪的形成机制之。     

IL-10在老年LN患者外周血单核细胞中的表达及意义

目的　研究白细胞介素 10 (IL 10 )在老年狼疮性肾炎 (LN)患者外周血单核细胞中的表达。 方法　采用逆转录聚合酶链反应 (RT PCR)法及流式细胞仪免疫荧光方法测定 2 0例老年LN病人外周血单核细胞IL 10mRNA及蛋白水平表达。 结果　老年LN病人外周血单核细胞IL 10mRNA及蛋白表达均明显高于正常老年人 ,且活动期又高于非活动期 ,IL 10mRNA表达与蛋白表达间有明显正相关。 结论 　老年LN外周血单个核细胞中IL 10mRNA和蛋白表达增加 ,与LN活动性密切相关。提示老年LN病人外周血单核细胞IL 10过度表达与LN的发病及活动性有关。     

系统性红斑狼疮外周血单个核细胞DcR3 mRNA表达研究

目的研究凋亡相关基因诱骗受体3(DcR3)在系统性红斑狼疮患者(SLE)外周血单个核细胞(PBMCs)中的mRNA表达水平。方法应用半定量逆转录-聚合酶链反应(RT-PCR)检测38例SLE患者(21例活动期,17例缓解期)和15例正常人PBMCs中DcR3 mRNA的表达水平,分析其与狼疮活动指数(SLEDAI)的相关性。结果SLE患者PBMCs中,DcR3mRNA表达水平明显高于正常人(P<0.01),但疾病不同病期(活动期与缓解期)其表达水平无统计学差异(P>0.05);DcR3 mRNA表达与SLEDAI不相关(r=-0.024,P>0.05)。结论SLE患者PBMCs DcR3 mRNA表达增加,提示DcR3可能与SLE免疫细胞凋亡异常和免疫调节的紊乱有关,参与了SLE的发病过程。     

转化生长因子βⅡ型受体在狼疮肾炎患者外周血单个核细胞表达的意义

目的 探讨狼疮肾炎(LN)患者外周血单个核细胞(PBMCs)转化生长因子βⅡ型受体(TβR Ⅱ) mRNA表达水平及其与疾病活动性的关系.方法 应用反转录-聚合酶链反应(RT-PCR)法检测44=例LN患者(均为活动期患者)、21例其他非LN患者和40名健康对照组PBMCs中TβRⅡ mRNA的表达水平,LN患者中未使用与使用激素和(或)免疫抑制剂患者分别为16例和28例.结果 LN患者PBMC中T13R H mRNA水平1.7±1.0显著低于非LN组4.0±3.1及健康对照组4.1±2.5(P<0.01);LN患者中未使用激素和(或)免疫抑制剂组T13R H mRNA的表达水平1.3±1.0低于用药组2.0+0.9(P<0.05);LN患者PBMCs中的T13RII mRNA表达水平与系统性红斑狼疮疾病活动指数(SLEDAI)评分标准(r-0.309,P<0.05)及抗双链DNA抗体(r-0.401,P<0.01)呈显著负相关,与补体C3呈显著正相关(r=0.621,P<0.01).结论 LN患者PBMCs中的TβRⅡmRNA表达水平降低,TβRⅡ参与了LN的发病过程,并与疾病的活动性显著相关;应用激素和(或)免疫抑制剂可以提高TTβRⅡ mRNA的表达,减轻炎症损害.     

白细胞介素-17在狼疮性肾炎外周血单个核细胞上的表达及意义

目的　探讨白细胞介素 - 17(IL - 17)在狼疮性肾炎患者 (LN)外周血单个核细胞 (PBMC)表达和分泌及其与LN疾病活动性的关系。方法　用酶联免疫吸附法 (ELISA)检测LN活动期患者血浆及PBMC体外自发培养或刺激培养的上清液中IL - 17蛋白水平 ,流式细胞仪免疫荧光分析法检测PBMC表达IL - 17的水平 ;用逆转录 -聚合酶联反应 (RT -PCR)法测定LN活动期患者PBMC体外自发培养和刺激培养后的IL - 17mRNA的表达水平。结果　LN活动期患者血浆检测不出IL - 17(<5ng/L) ;PBMC自发培养和PHA刺激培养下 ,LN活动期、LN静止期和正常对照 ,三组均检测不出IL - 17;而PBMC在CD3mAb +CD2 8mAb和PMA +ionomycin刺激培养下 ,较自发培养和PHA刺激培养 ,上述 3组IL - 17水平均明显升高 (P <0 .0 1) ,LN活动期PBMC表达、分泌IL - 17水平与SLE疾病活动指数 (SLEDAI)呈明显正相关。结论　LN活动期患者PBMC表达、分泌IL -17水平存在明显异常 ,并能反映LN疾病活动程度     

依那普利对实验性心肌梗死大鼠左室gp13O基因表达的影响

目的:研究急性心肌梗死(AMI)后左室重塑(LVRM)的发生与gp130基因异常表达的关系及依那普利对gp130表达的影响.方法:AMI后24h存活的73只雄性Wistar大鼠随机分为AMI组及依那普利治疗组,AMI组又依照术后1、3、7、14、21、28 d分为6个时间点,另设假手术组及正常对照组.各8只.依那普利组于术后第2天起灌胃给药(10mg·kg-1·d-1),连续4周.行心脏标本病理分析,分别采用放射免疫法和氯氨T法测定左室非梗死区(LVNIZ)血管紧张素Ⅱ(AngⅡ)和LVNIZ羟脯氨酸含量(HC),用RT-PCR法检测LVNIZ gp130 mRNA的表达.最终获完整资料大鼠76只,于上述各组分别为9、8、8、9、9、8、9、8和8只.结果:①与正常及假手术组相比,AMI组LVRM参数:心脏重量(HW)、左室重量(LVW)、左室重量指数(LVWI)、心肌细胞横径(TDM)、HC均显著增加(P＜0.05～0.01);②AMI组LVNIZ AngⅡ明显升高,与LVRM相关性好(P＜0.01);③LVNIZ gp130 mRNA表达于AMI第1天即开始明显增加,第7天达高峰,以后有所下降,但第28天时仍明显高于对照组(P＜0.05～0.01);④相关分析显示LVNIZ gp130mRNA表达水平与LVNIZ AngⅡ、LVRM 参数间呈正相关(P＜0.05～0.01);⑤与AMI第28天组相比,依那普利组LVRM明显减轻,LVNIZAngⅡ显著下降,gp130 mRNA表达明显下调(P＜0.05～0.01).结论:大鼠AMI后LVNIZ gp130 mRNA的过度表达与AMI后LVRM的发生密切相关,依那普利改善LVRM的机制还可能与抑制gp130基因的过度表达有关.     

狼疮肾炎患者肾组织白细胞介素-18表达的研究

目的　初步探讨白细胞介素 18(IL 18)在人类狼疮肾炎 (LN)肾组织炎症损伤中的作用。方法　应用免疫组织化学和原位杂交技术观察 6例正常肾组织和 18例LN患者肾组织IL 18的蛋白和基因表达量 ,并用酶联免疫吸附测定 (ELISA)法对该组患者尿IL 18水平进行检测。结果　正常肾组织有弱的IL 18mRNA及蛋白表达 ;LN患者肾组织IL 18mRNA及蛋白表达量均较正常肾组织显著增高 (IL 18mRNA :8 9± 3 4比 2 2± 0 6 ;IL 18蛋白 :8 8± 3 7比 1 4± 0 4 ) ,而且WHOⅣ型LN患者肾组织IL 18表达量显著高于非WHOⅣ型LN患者 (IL 18mRNA :10 8± 3 2比6 6± 1 7;IL 18蛋白 :11 2± 2 7比 5 6± 2 0 ) ;Spearman相关分析提示肾组织IL 18蛋白表达量与狼疮肾炎肾组织活动指数 (AI)、尿IL 18水平及肾组织损伤程度均呈正相关 (P均 <0 0 5 )。结论　肾内IL 18表达上调参与LN肾组织炎症损伤过程 ,尿IL 18水平可能作为衡量LN肾组织炎症活动程度的评估指标。     

糖皮质激素受体α在系统性红斑狼疮发病机制中的作用研究

目的探讨系统性红斑狼疮(SLE)患者外周血单个核细胞(PBMCs)糖皮质激素受体!(GR!)mRNA表达及其与免疫指标[抗核抗体(ANA)、抗dsDNA抗体]的变化、疾病活动性的关系,分析GR!在SLE发病机制中的作用。方法采用反转录聚合酶链反应(RT-PCR)检测活动期和缓解期SLE患者和正常人PBMCs中GR!mRNA的表达,并将其与ANA、抗dsDNA抗体及疾病活动性作相关分析。结果SLE患者PBMCs中GR!mRNA表达较正常人明显减少(P<0.05),但活动期患者表达高于缓解期患者(P<0.05),且与抗dsDNA抗体及疾病活动性呈负相关。结论SLE患者外周血PBMCs存在GR!的表达缺陷,从而引起对自身反应性T、B淋巴细胞的活化缺乏抑制效应,导致自身免疫耐受丧失,产生炎症性细胞因子和自身抗体。GR!在SLE的发病机制中可能发挥重要作用。     

Functional interaction of the gp80 and gp130IL-6 receptors in human B cell malignancies

IL-6, or cytokines of the IL-6 family using gp130 as transducer chain receptor, have been suggested to play a role in certain B lymphoid neoplasia. The presence of cell membrane gp80 and gp130 IL-6 receptors was studied in 98 patients with various leukaemia and non-Hodgkin's malignant lymphoma using flow cytofluorometry and immunohistology. Except neoplasia of immature B cells which expressed neither of the receptors, the majority of B cell tumours expressed one or both of them, mantle cell lymphoma being found to express the highest density of receptors. Using IL-6-dependent XG myeloma cell lines and mAb recog-nizing various gp80 and gp130 functional epitopes, it has been shown that IL-6 activation leads to a modified expression of some epitopes. In particular, the decrease or the dis-appearance of a gp130 epitope called A1 signed gp130 dimerization which is the first step of the gp130 activation pathway. Gp80 and gp130 epitope analysis was achieved in 17 of the patients. In four, an epitope phenotype compatible with a cytokine-induced activation was found. The cells of five B-CLL patients which expressed both gp80 and gp130 receptors were incubated with IL-6 to induce activation. In three of the cases they were found to rearrange their receptors in activated forms but not in the two others, showing that cells able to be activated or not can be found. These results confirm that gp130 signalling might play an important role in the pathogenesis of certain B cell neoplasia.     

Circulating interleukin-6 family cytokines and their receptors in patients with congestive heart failure

gp130 is a common signal-transducing receptor subunit for the interleukin (IL)-6 cytokine family. Studies in genetically engineered animal models have demonstrated a critical role for the gp130-dependent cardiomyocyte survival pathway in the transition to heart failure. In the present study, we examined plasma levels of the IL-6 family of cytokines and the soluble form of their receptors in patients with congestive heart failure (CHF). Circulating levels of the IL-6 family of cytokines, soluble IL-6 receptor (sIL-6R), and soluble gp130 (sgp130) were examined in 48 patients with various degrees of CHF, including dilated cardiomyopathy (DCM), ischemic cardiomyopathy (ICM), and valvular cardiomyopathy (VCM). Circulating levels of IL-6, leukemia inhibitory factor (LIF), and sgp130 significantly increased in association with the severity of CHF. No significant difference was observed in the circulating levels of sIL-6R and IL-11 among these patients. Interestingly, DCM patients showed higher circulating sgp130 levels than patients with ICM or VCM. Our findings suggest that gp130 expression in the heart is likely to be dynamic, and that the IL-6 family of cytokines and their common receptor gp130 participates in the pathogenesis of CHF, especially in DCM.     

疮性肾炎患者淋巴细胞白细胞介素-6受体 （CD126与CDw130）分布的研究

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白细胞介素-6及其受体在系统性红斑狼疮患者外周血中的表达

目的 了解系统性红斑狼疮（ＳＬＥ）患者血清白细胞介素－６（ＩＬ－６）和可溶笥白细胞介素－６受体（ｓＩＬ－６Ｒ水平及其与临床活动性指标的相关性,并初步探讨其ＩＬ－６信号传导途径。方法 采用ＭＴＴ比色法和酶联免疫吸附实验（ＥＬＩＳＡ）法分别检测１６例ＳＬＥ（９例活动,７例非活动）、１７例活动期类风湿关节炎（ＲＡ）患者及２９例正常人血清ＩＬ－６和ｓＩＬ－６Ｒ水平。并在体外用ＩＬ－６刺激分离单个核细胞后,     

Expression and regulation of gp130 messenger ribonucleic acid in cultured immature rat Sertoli cells

The expression of glycoprotein 130 (gp130) was studied in rat primary Sertoli cells by Northern blot analysis. Gp130 mRNA of 9.0 and 7.5 kb were detected in a variety of rat tissues including the testis. Gp130 mRNAs were detected in isolated, immature Sertoli cells. The levels of gp130 were significantly stimulated by the addition of interleukin-1-beta (IL-1-beta) or interleukin-6 (IL-6) but not by the addition of follicle-stimulating hormone (FSH). IL-6 activates intracellular signaling by binding with a receptor consisting of an 80-kDa ligand-binding protein, IL-6 receptor (IL-6R), and a second 130-kDa protein, gp130. As previously reported, expression of IL-6R mRNA in rat Sertoli cells was stimulated not only by IL-1-beta and IL-6 but also by FSH. In contrast, gp130 mRNA expression was not stimulated by FSH in our analysis. These data suggest that gp130 expression may be regulated by more than 1 mechanism and that production of gp130 and IL-6R, the 2 components of the IL-6 receptor system, may be regulated, at least in part, by a different pathway.     

CD3单抗和淋巴细胞功能相关抗原-1对狼疮肾炎外周血单个核细胞的共刺激作用

目的：探讨CD3单抗（mAb)和淋巴细胞功能相关抗原－1单抗（LFA－1mAb)对狼疮肾炎（LN）患者外周血单个核细胞（PBMC）的共刺激作用。方法：2例LN患者被分为活动期（n=14)和非活动期（n=15)，以12例健康献血员为对照，观察CD3mAb或（和）LFA－1mAb共刺激及阻断1－磷酯酰肌醇3－激酶（PI3－K）对体外培养96h后PBMC增生和IL－2产生的影响。PBMC提取采用Ficoll密度梯度离心法，细胞增生实验采用^3H-TdR掺入法，IL－2测定采用ELISA法。结果：PBMC培养96h后，自然生长的LN非活动期和活动期PBMC ^3H-TdR掺入量和IL－2合成与正常对照无明显差异（P值均＞0或0．05）；与自然生长的PBMC相比，CD3mAb单独处理增加了LN非活动期（P值均＜0．05）和活动期（P值均＜0．05）PBMC^3H-TdR掺入量和IL－2合成。而单独CD3mAb对正常对照PBMC^3H-TdR掺入量和IL－2合成没有影响（P值均＞0．05）。与CD3mAb单独处理组相比，CD3mAb和LFA－1mAb共刺激均增加了LN活动期（P值均＜0．05）和非活动期（P值均＜0．05）及正常对照（P值均＜0．05）PBMC ^3H-TdR掺入量和IL－2合成；与对照组相比，CD3mAb和LFA－1mAb共刺激后活动期（P值均＜0．01）和非活动期（P值均＜0．01）PBMC^3H-TdR掺入量和IL－2合成均增加，但活动期效应明显强于非活动期（P＜0．01）。PI3－K特异抑制剂Wortmannin(WT)的加入明显抑制了CD3mAb和LFA－1mAb共刺激诱导的PBMC增生和IL－2的分泌效应（P＜0．01，P＜0．01）。结论：CD3和FLA－1对狼疮肾炎PBMC具有共刺激作用，这种共刺激作用可能参与了狼疮肾炎T、B细胞的异常活化，阻断共刺激传递信号分子PI3－K则能抑制CD3和LFA－1介导的共刺激作用。