Fas and Fas ligand gene expression in autoimmune thyroiditis in BB/W rats

OBJECTIVE: Apoptosis via the Fas pathway is a potential mechanism for thyroid tissue destruction leading to clinical hypothyroidism in Hashimoto's thyroiditis (HT). Recent studies reported contradictory results regarding the regulation of Fas/Fas ligand (FasL) expression by cytokines in vitro. We therefore determined the Fas and FasL gene expression in the BioBreeding/Worcester (BB/W) rat thyroiditis model, which can be regarded as a model for HT. METHODS: In order to obtain BB/W rats with spontaneous, iodine-induced or without lymphocytic thyroiditis (LT), rats were divided into 3 groups: 55-day-old rats after 24 days of iodine administration, 75-day-old rats after 45 days of iodine administration, and 101-day-old rats respectively. The gene expression of Fas, FasL, and interleukin (IL)-1beta was determined by Genescan fragment analysis using reverse polymerase chain reaction. Serum thyroglobulin (TG) antibody concentrations were measured and the extent of lymphocytic infiltration of one thyroid lobe was histologically graded. RESULTS: Fas and FasL gene expression was significantly higher in rats with LT and correlated with the extent of lymphocytic infiltration and the TG antibody level. There was no evidence that the expression of IL-1beta or other cytokines is related to the expression of Fas or its ligand. CONCLUSIONS: The increased expression of Fas and FasL in LT of BB/W rats suggests the involvement of the Fas pathway in the pathogenesis of LT in BB/W rats. However, in contrast to results of recent in vitro studies, in the BB/W rat Fas/FasL expression is not regulated by IL-2, -4, -6, -10, -12, interferon gamma, and tumor necrosis factor alpha.     

NOD小鼠口服胰岛素对胰岛Fas及其配体表达的影响

目的观察口服胰岛素对ＮＯＤ小鼠糖尿病和胰岛炎发生情况的影响以及观察口服免疫耐受后胰岛Ｆａｓ和Ｆａｓ配体（ＦａｓＬ）表达的改变情况。方法将雌性ＮＯＤ小鼠６４只,随机分为两组：一组（３０只）给予磷酸缓冲液（ＰＢＳ）５００μｌ,另一组（３４只）给予胰岛素１ｍｇ加ＰＢＳ５００μｌ,５周龄开始给药,第１周两次,以后每周一次至３０周。采用免疫组化染色法观察了口服免疫耐受治疗后ＮＯＤ小鼠胰岛组织Ｆａｓ和ＦａｓＬ的改变情况。结果口服胰岛素能明显减少胰岛炎和糖尿病的发生,对照组１４周龄即出现糖尿病而胰岛素组２６周龄才出现糖尿病,２６周龄时两组的发病率分别为１１％和７９％（Ｐ＜０．００１）,Ｆａｓ出现在糖尿病小鼠而ＦａｓＬ出现在胰岛素喂饲后的小鼠。结论口服胰岛素能明显减少胰岛炎和糖尿病的发生,口服胰岛素诱导的ＦａｓＬ表达在胰岛素阻止糖尿病和胰岛炎的发生机制中起一定的作用     

Prevalence of HLA-DRB1 genotype and altered Fas/Fas ligand expression in adrenocortical carcinoma

A distinctive feature of malignant adrenocortical neoplasms is decreased major histocompatibility complex (MHC) class II molecule expression. However, it is unknown whether there exists a restriction to certain MHC genotypes and whether this involves alterations of the Fas/Fas ligand system and thereby affects tissue homeostasis. Therefore, MHC class II phenotype and genotype and expression patterns of the Fas/Fas ligand system were investigated in 24 adrenocortical tumors (n(Adenomas) = 14, n(Carcinomas) = 10) and an adrenal cancer cell line (NCI-H295). No MHC class II antigen expression was detected in carcinomas. The DRB1*01 genotype was found in 54.5% of patients with carcinoma (P = 0.046). No prevalence of any genotype could be detected in patients with adenomas, which exhibited varying levels of antigen expression. Fas receptor expression was 75.0% in adenomas compared with 20.0% in carcinomas (P = 0.0196), whereas ligand expression was 37.7% in adenomas and reached almost 100% in the carcinomas investigated in this study (P = 0.0033). In summary, the DRB1*01 genotype may be correlated to a higher risk for malignancy. Additional studies on MHC class II genotype and phenotype and the altered Fas/Fas ligand system in adrenal neoplasms may help to identify mechanisms of immune escape and suggest new diagnostic approaches.     

38例急性乙型病毒性肝炎肝组织中Fas抗原和Fas配体的表达研究

目的:探讨Fas-FasL系统在急性病毒性肝炎发病中的作用.方法:采用免疫组织化学技术.结果:38例急性乙型肝炎肝组织中的Fas和FasL表达的检出率分别为55.3%和66.5%;Fas和FasL的表达强度与患者的年龄、性别和血清A、A/G和PTA无关,而与血清ALT和TBIL水平有关.较重型(伴桥样坏死)的急性乙型肝炎其Fas和FasL表达比轻型急性乙型肝炎要强.结论:由CTL-Fas-FasL系统介导的肝细胞凋亡在急性乙型肝炎的发病中起了较重要的作用.     

Fas and Fas ligand expression in fetal and adult human testis with normal or deranged spermatogenesis

In mice, the Fas/Fas ligand (FasL) system has been shown to be involved in germ cell apoptosis. In the present study we evaluated the expression of Fas and Fas ligand (FasL) in fetal and adult human testis. Semiquantitative RT-PCR demonstrated the expression of Fas and FasL messenger ribonucleic acids in adult testis, but not in fetal testis (20-22 weeks gestation). In situ RT-PCR and immunohistochemistry experiments on adult human testis demonstrated the expression of FasL messenger ribonucleic acid and protein in Sertoli and Leydig cells, whereas the expression of Fas was confined to the Leydig cells and sporadic degenerating spermatocytes. The number of Fas-positive germ cells per 100 Sertoli cell nuclei was increased in 10 biopsies with postmeiotic germ cell arrest compared to 10 normal testis biopsies (mean, 3.82 +/- 0.45 vs. 2.02 +/- 0.29; P = 0.0001), but not in 10 biopsies with meiotic germ cell arrest (mean, 1.56 +/- 1.07). Fas and FasL proteins were not expressed in cases of idiopathic hypogonadotropic hypogonadism. Together, these findings may suggest that Fas/FasL expression in the human testis is developmentally regulated and under gonadotropin control. The increased germ cell expression of Fas in patients with postmeiotic germ cell arrest suggests that the Fas/FasL system may be involved in the quality control mechanism of the produced gametes.     

Estradiol increases apoptosis in human coronary artery endothelial cells by up-regulating Fas and Fas ligand expression

CONTEXT: In animal models, estrogen inhibits atherogenesis by inhibiting many of the early steps of atherosclerotic plaque formation. However, the lack of cardioprotective effect by postmenopausal hormone replacement therapy and possible increase in cardiovascular events observed during the first year after the initiation of hormone replacement therapy may suggest that once the plaque is formed, estrogen may have additional effects that may counteract its beneficial outcomes. Indeed, the effect of estrogen on plaque stability has not been identified. OBJECTIVE: We hypothesized that 17beta-estradiol (E2) may cause increased apoptosis in human coronary artery endothelial cells (HCAECs). This effect would explain an adverse effect on plaque stability in vivo. INTERVENTION(S) AND MAIN OUTCOME MEASURE(S): The effect of E2 on apoptosis, cell proliferation, and expression of proapoptotic molecules Fas and Fas ligand (FasL) in cultured HCAECs was evaluated. RESULTS: HCAECs in culture treated with E2 showed an increase in DNA strand breaks and nuclear fragmentation indicative of apoptosis. E2 treatment also induced a significant concentration-dependent increase in Fas mRNA and protein expressions in HCAECs. Moreover, the expression of FasL mRNA and secretion of FasL protein by HCAECs were enhanced in response to E2 treatments. CONCLUSIONS: E2 increases the apoptosis in cultured HCAECs. Enhanced Fas and FasL expressions in response to E2 suggest that activation of the Fas/FasL pathway may be a mediator of the proapoptotic effects of E2 in these cells.     

E-钙黏附素和β-连环素在胰腺上皮内瘤变和胰腺癌组织中的表达

目的:探讨胰腺上皮内瘤变PanIN和胰腺癌组织中E-钙黏附素(E-Cad)和β-连环素(β-Cat)异常表达的意义.方法:回顾性研究长海医院2001-01/2003-12间外科切除和同期尸检的156例胰腺标本,并构建了组织芯片,其中含有129灶PanIN-1A,104灶PanIN-1B,22灶PanIN-2,11灶PanIN-3和121例导管腺癌和相应癌旁组织.用EnVision免疫组化技术检测上述病变组织中E-Cad和β-Cat的表达变化,并结合临床病理资料进行相关分析.结果:导管腺癌中E-Cad异常表达率明显高于PanINs和正常导管(64.5%,32.3%,0%),且与胰腺癌的分化程度、淋巴结转移和神经浸润密切相关(P＜0.05).PanINs和导管腺癌中E-Cad胞质表达较正常导管明显增加.β-Cat的异常表达与胰腺癌淋巴结转移和神经浸润有明显相关性(P＜0.05).高级别PanINs和导管腺癌中β-Cat胞质和胞核的表达率明显高于低级别PanINs和正常导管(P＜0.05).PanINs和导管腺癌中E-Cad和β-Cat表达间呈正相关性(P＜0.01,P＜0.05).结论:胰腺癌和PanINs中E-Cad和β-Cat的异常改变提示他们不仅与胰腺癌的生物学行为和预后有关,而且也参与了胰腺癌的发生.     

sFas与sFasL在自身免疫疾病中的意义

目的　研究sFas与sFasL在系统性红斑狼疮 (SLE)等自身免疫疾病中的意义及抗单链DNA(ssDNA)抗体与sFas和sFasL介导凋亡的相关性。方法　采用夹心ELISA方法检测 31例SLE病人 ,32例类风湿关节炎 (RA)病人 ,2 0例 1型糖尿病 (IDDM )病人及 5例多发性硬化病 (MS)病人血清中sFas与sFasL含量及抗ssDNA抗体水平。结果　在SLE、RA、IDDM及MS患者血清中的sFas含量 (pg/ml)分别为 2 881± 16 5 3 ,988± 6 96 ,135 2± 413 ,15 40± 5 6 6 ,明显高于正常对照 (P <0 0 0 2 ) ,SLE病人sFas含量高于RA ,MS ,IDDM病人。SLE、RA患者血清sFasL含量 (pg/ml)分别为5 35± 431、12 38± 1184,明显高于正常对照 (P <0 0 2 ) ,MS、IDDM患者血清sFasL含量 (pg/ml)分别为 2 5 1± 140 ,2 11± 73 ,低于正常对照 (P >0 0 5 )。在SLE、RA病人中 ,高浓度sFasL者伴有高浓度sFas。在SLE病人中 ,所有抗ssDNA抗体阳性者均伴有高浓度sFas,所有抗sFas阴性者 ,ssDNA抗体也为阴性。结论　在SLE等疾病中sFas水平明显高于正常人 ,可作为疾病进展与治疗效果的判断指标。抗ssDNA抗体与sFas具有关联性。sFas与sFasL在疾病中的相互作用及动态变化有待进一步研究     

Fas/FasL系统与胃癌

Fas抗原是细胞表面重要的死亡受体之一,Fas与相应配体（FasL)相结合是诱导细胞凋亡的重要途径之一,而肿瘤的发生不仅有细胞增殖的异常,也存在细胞凋亡的异常,近年来为了阐明胃癌发生过程中细胞凋亡异常的分子机制,对Fas/FasL系统在胃癌及癌前病变中的表达和作用进行了深入研究,现将有关的研究进展综述如下。     

ALK expression is absent in pancreatic ductal adenocarcinoma

Purpose

It has not yet been clearly defined whether anaplastic lymphoma kinase (ALK) expression can be detected in pancreatic ductal adenocarcinoma (PDAC).

Methods

Within a retrospective study, archival PDAC surgical specimens were screened for ALK expression in tumor and normal tissue by immunohistochemistry (IHC) with the use of a specific ALK detection kit on a tissue microarray (TMA).

Results

PDAC tumor tissue was available from 99 resected cases: fifty-eight out of 99 patients (59 %) had nodal-positive disease, and 80 patients (81 %) had pT3 tumors. Forty-nine patients underwent R0 resection, and in 48 cases, resection status was classified R1. Regarding ALK expression, five cases showed faint immunoreactivity on TMA, which was negative on whole mount sections. All other 94 cases showed no ALK expression.

Conclusion

In 99 PDAC cases, no ALK expression was detected by IHC; ALK thus may not serve as a relevant drug target in PDAC.     

加强Fas和Fas配体的研究

加强Ｆａｓ和Ｆａｓ配体的研究贾克明Ｆａｓ是人体多种细胞表面的一种膜蛋白，具有３２５个氨基酸，Ｆａｓ基因位于人体第１０对染色体。Ｆａｓ配体（Ｆａｓｌｉｇａｎｄ或ＦａｓＬ）也是细胞表面的一种膜蛋白，具有２１８个氨基酸，其基因位于人体第１对染色体。当某一细...