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101.
Caigan Du Jifu Jiang Qiunong Guan Ziqin Yin Mark Masterson Anwar Parbtani Robert Zhong Anthony M. Jevnikar 《American journal of transplantation》2004,4(10):1583-1594
Tubular epithelial cells (TECs) coexpress Fas and Fas ligand (FasL), which could influence renal allograft injury. While TECs can resist apoptosis by Fas antibody, TEC apoptosis by contact with adjacent TECs has not been studied. Fas expression increased in TECs with cytokine treatment (IFN-gamma, TNF-alpha) while abundant FasL levels were not altered. Apoptosis (Annexin-V, DNA fragmentation) occurred in cytokine-treated TECs monolayers from C3H-HeJ mice by 24 h, but was absent in similarly treated TECs from Fas-deficient (lpr) or FasL-mutant (gld) mice, suggesting that 'self injury' occurred through Fas/FasL. Membrane labeling of TECs in cocultures confirmed that FasL-bearing TECs induced apoptosis when in contact with Fas-bearing TECs. Culturing TECs with allogeneic C57BL/6 (H-2b) splenocytes resulted in apoptosis and elimination of C3H-HeJ TECs by 48 h, with enhanced survival and reduced apoptosis using lpr or gld TECs. In a renal allograft model, survival of C57BL/6 recipients was greater (p < 0.05) and renal function improved (p < 0.001) using C3H-lpr or C3H-gld (H-2 k) donor kidneys compared with C3H-HeJ kidneys. These data demonstrate for the first time that cytokine-activated TECs can injure TECs through expression of functional FasL and Fas. We suggest that inhibition of TEC-TEC 'self injury' may be a novel strategy to augment renal allograft survival. 相似文献
102.
HLA-G和Fas配体在肾透明细胞癌中的表达及意义 总被引:2,自引:0,他引:2
目的:探讨两种免疫抑制分子人类白细胞表面抗原HLA—G和Fas配体(FasL)与经典型肾透明细胞癌(ccRCC)分级和分期的相关性。方法:采用免疫组织化学方法对60例ccRCC标本石蜡切片进行检测,数据由SPSS软件进行统计分析。结果:肿瘤旁正常肾组织中无HLA—G表达;肾癌组织中,40例(66.7%)表达HLA—G,36例(60.0%)表达FasL。31例(51.7%)两者均表达,15例(25.0%)两者均不表达。在同一标本中,肿瘤侵犯脉管或淋巴结后,其HLA-G或FasL表达较原位肿瘤明显增强。统计分析显示HLA—G表达的阳性率和表达强度与肿瘤的分期、分级均呈正相关(P〈0.01)。FasL表达的阳性率与肿瘤分级呈正相关(P〈0.05),而表达强度与肿瘤分期呈正相关(P〈0.01)。结论:ccRCC中HLAG和FasL的表达与肿瘤的分期、分级均呈正相关,与淋巴结转移有一定关系;晚期ccRCC高表达免疫抑制分子的机制需进一步研究。 相似文献
103.
目的 :探讨急性白血病患者血循环中 s Fas、s Fas L 及 s ICAM- 1水平变化的关系。方法 :采用酶联免疫吸附试验(EL ISA)对 5 0例急性白血病患者的血清 s Fas、s Fas L 及 s ICAM- 1水平进行同步检测 ,比较其水平变化的相关性。结果 :血清 s Fas、s Fas L及 s ICAM- 1的测定值 (x± s,μg/L )分别为 :初治前急性淋巴细胞白血病 (AL L ) (3.84± 1.32 ,0 .2 4± 0 .0 8及 10 5 8± 114 )和急性髓性白血病 (AML) (3.4 0± 0 .4 0 ,0 .2 3± 0 .11及 10 0 8± 84 ) ,未缓解 /复发 AL L(3.33± 0 .95 ,0 .2 3± 0 .0 9及 885± 14 6 )和 AML (3.4 8± 1.0 2 ,0 .2 5± 0 .0 8及 910± 10 4 ) ,均明显高于完全缓解 (CR)或部分缓解 (PR) AL L(2 .6 4± 0 .6 2 ,0 .15± 0 .0 6及 5 6 7± 15 5 )和 AML(2 .4 1± 0 .4 8,0 .15± 0 .0 5及 4 93± 76 )及正常对照 (2 .6 5± 0 .37,0 .13± 0 .0 5及 5 78± 16 8) (P<0 .0 1或 P<0 .0 5 ) ;此 3个变量间的相互比较 ,未见明显相关性 (P>0 .0 5 )。结论 :血清 s Fas、s Fas L或 s ICAM- 1水平的测定可用于评价急性白血病的病理状态及转归 ,联合检测这些分子也许更有临床价值。 相似文献
104.
Ki67、Fas系统在卵巢肿瘤组织中的表达及临床意义 总被引:5,自引:0,他引:5
目的:通过检测卵巢肿瘤组织Ki67,Fas系统的表达,探讨其与卵巢细胞增殖与凋亡的关系。方法:用流式细胞术检测Ki67,Fas,FasL抗原在52例卵巢肿瘤组织中的表达。结果:(1)卵巢癌组织中Ki67表达显著高于卵巢良性肿瘤(P<0.01),Fas表达下调(P<0.01),FasL表达增高(P<0.01),(2)Ki67随组织学分级(P<0.01),临床分期(P<0.05)的升高而增加,与卵巢癌组织大小呈正相关(r=0.499,P=0.006),与淋巴结转移无关,Fas与组织学分级,临床分期,淋巴结转移及组织大小无关(P>0.05),FasL的表达与临床分期无关,但随组织学分级的升高而增加(P<0.05),有淋巴结转移者FasL的表达高于无淋巴结转移者(P<0.05),结论:Ki67与卵巢癌的组织学分级,临床分期及肿瘤大小有关,卵巢癌组织中存在Fas表达的下调及FasL表达增加,这与肿瘤的免疫逃逸有关。 相似文献
105.
131I对甲状腺细胞凋亡的影响 总被引:1,自引:0,他引:1
由于每个患者特异性基因决定的个体辐射敏感性不同,使得每个接受131I治疗的患者对治疗的反应不一,因而疗效差异较大.针对不同的个体,采用不同的剂量治疗才可以提高131I治疗的效率,降低甲状腺功能减退症的发病率.通过目前的分子生物学技术,我们已经了解到一些基因的蛋白表达产物(Fas/FasL、Bcl-2等)与细胞凋亡和射线诱导凋亡的联系,使对凋亡基因表达产物的体外监测成为可能.也许通过对这些指标的监测,可以使我们在131I治疗过程中实现对不同的个体给予恰当的个体剂量. 相似文献
106.
肺癌组织Fas和FasL表达及临床意义 总被引:3,自引:0,他引:3
目的:研究肺癌组织中Fas和FasL表达及临床意义。方法:采用免疫组化SP法对46例肺癌组织和30例癌旁肺组织进行Fas和FasL表达检测。结果:在肺癌组织中,Fas表达下调,FasL表达明显上调。Fas在鳞癌、腺癌和小细胞肺癌中表达水平显低于癌旁肺组织(P<0.01),且与肺癌的病理分级、临床分期及转移呈负相关(P<0.05)。分化程度低、已发生转移的肺癌Fas表达水平显下调(P<0.05)。而FasL在鳞癌、腺癌和小细胞肺癌中表达水平显高于癌旁肺组织(P<0.05),且与肺癌的病理分级、临床分期及转移呈正相关(P<0.05)。分化程度低、临床分期晚及已发生转移的肺癌FasL表达水平明显上调(P<0.05)。Fas和FasL表达水平间呈负相关(P<0.05)。结论:肿瘤通过下调Fas、上调FasL这种表达异常在肺癌发生、发展及转移过程中可能起协同作用。Fas和FasL可能成为早期诊断肺癌的标志物之一,联合检测对判断肺癌恶性程度及预测预后有较大参考价值。 相似文献
107.
目的检测强直性脊柱炎(As)患者外周血T细胞亚群上的Fas/FasL的表达水平,探讨Fas/FasL诱导的细胞凋亡在As免疫学发病机制中的作用。方法以临床确诊的60例As患者作为研究对象,同时选择30例正常对照,运用流式细胞仪(FCM)检测其外周血CD3^+CD4^+、CD3^+CD8^+T细胞亚群上的Fas/FasL表达水平。结果早、晚期AS患者外周血CD3^+CD4^+T细胞上的FasL的表达率分别为(0.59%、0.93%),CD3^+CD8^+T细胞上的FasL的表达率分别为(2.93%、4.32%),与健康对照组(0.48%、1.14%)比较,其表达率差异具有统计学意义(P〈0.05);与健康对照组外周血CD3^+CD4’、CD3^+CD8’T细胞上的Fas表达率(58.25%、59.91%)比较,早期AS患者外周血CD3^+CD4^+T细胞上的Fas的表达率(64.75%)明显升高(P〈0.05),而CD3^+CD8^+T细胞上的Fas的表达率(48.64%)明显降低(P〈0.05),Fas在晚期AS患者外周血CD3^+CD4^+、CD3^+CD8^+T细胞上的表达率(57.63%、56.32%)无明显变化。结论Fas、FasL在外周血T细胞亚群上的表达水平与AS的病情发展阶段相关;Fas、FasL的异常表达所导致T细胞凋亡功能紊乱可能是AS发病的重要机制之一。 相似文献
108.
The therapeutic effect of Interleukin-18 on hypertrophic scar through inducing Fas ligand expression
Xin Le Wei-Wei Wu 《Burns : journal of the International Society for Burn Injuries》2021,47(2):430-438
ObjectiveAmong downstream interleukin-18 (IL-18) targets, Fas ligand (FasL) in particular, has been strongly implicated in many conditions. Our study aims to explore the role of IL-18 in hypertrophic scar through enhancing FasL expression.MethodsIL-18 expression in hypertrophic scar tissues and normal tissues were explored by immunohistochemistry, qRT-PCR and Western blotting, and the expression of IL-18 in normal skin fibroblasts and hypertrophic scar fibroblasts by immunofluorescence. Hypertrophic scar fibroblasts treated with recombinant human IL-18 (rhIL-18) were assessed with MTT, Annexin V-FITC/PI, qRT-PCR, ELISA and western blotting. In the hypertrophic scar of rabbit ears, rhIL-18 was injected to determine histological changes with HE and Masson staining. Additionally, the scars were rated based on contour and overall severity using a visual analog scale scores (VAS).ResultsIL-18 was decreased in hypertrophic scar tissues and fibroblasts compared to normal skin tissues and fibroblasts, respectively. Decreased proliferation and increased apoptosis of hypertrophic scar fibroblasts were found after rhIL-18 treatment with enhanced expression of FasL, sFasL FADD, Caspase-8, Caspase-9 and Caspase-3 in a dose-dependent manner. The VAS and thickness of scars in rabbit ears was decreased as time went on after rhIL-18 treatment, with decreases in scar elevation index (SEI) and the increases in FasL expression.ConclusionIL-18 curbs proliferation and promotes apoptosis of hypertrophic scar fibroblasts by enhancing FasL expression. IL-18is a potential target for treatment of hypertrophic scar. 相似文献
109.
110.
Kim MS Lee J So HS Lee KM Jung BH Chung SY Moon SR Kim NS Ko CB Kim HJ Kim YK Park R 《Immunopharmacology and immunotoxicology》2001,23(1):55-66
Mistletoe lectin-II, a major composition of Korean mistletoe (Viscum album coloratum), is known as a potent apoptosis inducer. The previous research has demonstrated that Korean mistletoe lectin-II induces apoptosis via c-Jun N terminal kinase (JNK) activation in human myeloid U937 cells. The purpose of this research is to prove the synergistic action of mistletoe lectin-II and interferon-γ (IFN-γ) in the apoptotic cytotoxicity of U937. When U937 cells were treated with mistletoe lectin-II after being differentiated by IFN-γ, the proteolytic activity of caspase-3 and 9 was markedly elevated and that of caspase-8 was prolonged for 18 hr. The activation of caspase-3-like protease requires the earlier cleavage of poly(ADP-ribose) polymerase(PARP). Caspase-1 was, however, not activated during the resting phase and nor in IFN-γ-differentiated U937 cells. Western blot analysis revealed that, in IFN-γ-differentiated U937 cells, the expression of Fas (CD95/APO-1) & Fas ligand(FasL) increases the apoptotic sensitivity against Mistletoe lectin-II. Fas (CD95/APO-1) & FasL were not significantly induced solely by mistletoe lectin-II. Furthermore the activity of JNK1 in U937 cells was also markedly increased with IFN-γ-differentiation, compared to that of the control. These results suggest that the IFN-γ-differentiation of U937 cells increases the susceptibility to mistletoe lectin-II-induced apoptosis. 相似文献