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101.
Iwasaki H Okamoto R Kato S Konishi K Mizutani H Yamada N Isaka N Nakano T Ito M 《Atherosclerosis》2008,198(1):22-28
Recently, it has become evident that elevated levels of plasminogen activator inhibitor-1 (PAI-1) are associated with myocardial infarction and stroke, especially in patients with diabetes. The molecular mechanisms involved in hyperglycemia-induced PAI-1 expression in bovine aortic endothelial cells (BAEC) were investigated. PAI-1 expression in BAEC was significantly increased in accordance with the concentration of glucose in media from 5.7 mM to 23 mM. Stimulation with high glucose (23 mM) significantly increased small GTPase Rho A activation. Pretreatment with a Rho-kinase inhibitor, Y-27632 (1-10 microM), significantly blocked high glucose-induced PAI-1 expression. NF-kappaB activity determined using the luciferase reporter gene assay was significantly enhanced by high glucose, and pretreatment with Y-27632 inhibited high glucose-induced PAI-1 expression at the basal level. An inhibitor of NF-kappaB action, namely parthenolide (0.1 microM), BAY 11-7082 (5 microM) and SN50 (1 microM), significantly blocked high glucose-mediated PAI-1 expression to a level with low glucose (5.7 mM). These data suggested that high glucose-induced PAI-1 expression in endothelial cells is mediated by NF-kappaB activation through the Rho/Rho-kinase pathway. Inhibition of Rho/Rho-kinase signaling might be a novel target for diabetes and metabolic syndrome. 相似文献
102.
Pietro Crivello Nina Lauterbach Laura Zito Federico Sizzano Cristina Toffalori Jessica Marcon Laura Curci Arend Mulder Lotte Wieten Elisabetta Zino Christien E.M. Voorter Marcel G.J. Tilanus Katharina Fleischhauer 《Human immunology》2013
The functional relevance of polymorphisms outside the peptide binding groove of HLA molecules is poorly understood. Here we have addressed this issue by studying HLA-DP3, a common antigen relevant for functional matching algorithms of unrelated hematopoietic stem cell transplantation (HSCT) encoded by two transmembrane (TM) region variants, DPB1*03:01 and DPB1*104:01. The two HLA-DP3 variants were found at a overall allelic frequency of 10.4% in 201 volunteer stem cell donors, at a ratio of 4.2:1. No significant differences were observed in cell surface expression levels of the two variants on B lymphoblastoid cell lines (BLCL), primary B cells or monocytes. Three different alloreactive T cell lines or clones showed similar levels of activation marker CD107a and/or CD137 upregulation in response to HLA-DP3 encoded by DPB1*03:01 and DPB1*104:01, either endogenously on BLCL or after lentiveral-vector mediated transfer into the same cellular background. These data provide, for the first time, direct evidence for a limited functional role of a TM region polymorphism on expression and allorecognition of HLA-DP3 and are compatible with the notion that the two variants can be considered as a single functional entity for unrelated stem cell donor selection. 相似文献
103.
《Autoimmunity》2013,46(3):162-172
AbstractSelf-specific B cells play a main role in the pathogenesis of lupus. This autoimmune disease is characterized by the generation of autoantibodies against self antigens, and the elimination of B and T cells involved in the pathological immune response is a logical approach for effective therapy. We have previously constructed a chimeric molecule by coupling a DNA-mimotope peptides to an anti-CD32 antibody. Using this protein molecule for the treatment of lupus-prone MRL/lpr mice, we suppressed selectively the autoreactive B-lymphocytes by cross-linking B cell receptors with the inhibitory FcγRIIb receptors. This approach was limited by the development of anti-chimeric antibodies in MRL mice. In order to avoid this problem, we established a murine severe combined immunodeficiency lupus model, allowing a long-term chimera therapy. Elimination of the double-stranded DNA-specific B cells by chimera therapy in MRL-transferred immunodeficient mice resulted in inhibition of T cell proliferation and prevented the appearance of IgG anti-DNA antibodies and of proteinuria. 相似文献
104.
目的:研究神经细胞黏附分子(neural cell adhesion molecule, NCAM)对小鼠黑色素瘤B16-F0细胞增殖的影响及其分子机制。方法:采用RNA干扰在B16-F0细胞中基因沉默NCAM,通过MTT和软琼脂克隆形成实验考察细胞增殖能力的变化;通过小鼠皮下肿瘤移植实验考察体内黑色素瘤生长的变化;使用免疫印迹筛选出受NCAM影响的信号分子,在此基础上使用RNA干扰和高表达实验确定介导NCAM调控增殖的主要信号分子。结果:NCAM基因沉默后B16-F0细胞的增殖能力和克隆形成能力明显降低,细胞在小鼠皮下形成的黑色素瘤的生长也明显受到抑制。其中,β-catenin介导了NCAM对于B16-F0细胞增殖的调控,但NCAM对于β-catenin的调控不依赖于经典的Wnt通路。结论:NCAM通过Wnt非依赖性的β-catenin通路促进小鼠黑色素瘤细胞的增殖。 相似文献
105.
106.
目的评价异氟醚和七氟醚吸入麻醉对肺癌根治术患者血清E-选择素(E-selectin)、内皮细胞间黏附分子(ICAM)-1、基质金属蛋白酶(MMP)-2、MMP-9浓度变化的影响。方法择期行肺癌根治术患者60例,年龄43~68岁,ASAⅠ或Ⅱ级。采用随机数字表法,将患者随机均分为两组:异氟醚(I组)和七氟醚组(S组)。两组患者气管插管后吸入1.7%~2.3%异氟醚或2.5%~3.4%七氟醚,维持I组异氟醚呼气末浓度为1.5~2.0 MAC、S组七氟醚呼气末浓度维持在1.5~2.0 MAC至术毕。于麻醉诱导前5min(T0)、手术开始后1h(T1)、手术开始后2h(T2)和术后1h(T3)时采集静脉血样,酶联免疫吸附法测定血清E-selectin、ICAM-1、MMP-2、MMP-9表达。结果与T0时比较,T1~T3时I组血清E-selectin、ICAM-1、MMP-2、MMP-9表达明显增加(P0.05),T2、T3时S组血清E-selectin、ICAM-1、MMP-2、MMP-9表达明显降低(P0.05)。T1~T3时S组血清E-selectin、ICAM-1、MMP-2、MMP-9表达明显低于I组(P0.05)。结论七氟醚能抑制肺癌根治术患者血清E-selectin、ICAM-1、MMP-2、MMP-9的表达。 相似文献
107.
A comparative phenotypical analysis of rheumatoid nodules and rheumatoid synovium with special reference to adhesion molecules and activation markers 总被引:11,自引:1,他引:11 下载免费PDF全文
D. Elewaut F. De Keyser N. De Wever D. Baeten N. Van Damme G. Verbruggen C. Cuvelier E. Veys 《Annals of the rheumatic diseases》1998,57(8):480-486
OBJECTIVES—(1)To analyse the in situ expression of adhesion molecules in rheumatoid nodules. (2) To compare the endothelial expression of adhesion molecules in synovial tissue and subcutaneous nodules obtained from the same patients. (3) To compare the expression of adhesion molecules and activation markers on T cell lines from nodules and synovium.
METHODS—(1) Immunohistochemical analysis by APAAP technique of E selectin, CD44, ICAM-1, PECAM-1, and VCAM-1 was performed on 10 rheumatoid nodules from seven patients with rheumatoid arthritis (RA); nodules and synovium were simultaneously analysed from three patients. (2) T cell lines were generated from RA nodules (n=7) and synovium (n=7) by interleukin 2 expansion, and subsequently characterised by flow cytometry for surface expression of αEβ7, α4β7, CD44, L selectin, LFA-1a, PECAM-1, and CD30.
RESULTS—(1) In rheumatoid nodules, the palisading layer strongly stains for ICAM-1 and PECAM-1, but less pronounced for CD44. VCAM-1 staining was usually negative. ICAM-1 is upregulated in the vessels surrounding the central zone of fibrinoid necrosis. The immunohistological picture in different nodules derived from the same patient was similar. (2) The endothelial expression of adhesion molecules is comparable in RA nodules and synovium on an individual level, except for E selectin, which is overexpressed in nodule endothelium. (3) T cell lines from nodules and synovium display similar adhesion molecule profiles. However, the expression of CD30, a T cell activation marker linked with Th2 subsets, is higher in nodules compared with synovium.
CONCLUSION—These data support a recirculation hypothesis of T cells between articular and extra-articular manifestations in RA, although the activation state of the T cells in each of these localisations may differ.
Keywords: T cells; adhesion molecules; rheumatoid nodules; rheumatoid synovium 相似文献
METHODS—(1) Immunohistochemical analysis by APAAP technique of E selectin, CD44, ICAM-1, PECAM-1, and VCAM-1 was performed on 10 rheumatoid nodules from seven patients with rheumatoid arthritis (RA); nodules and synovium were simultaneously analysed from three patients. (2) T cell lines were generated from RA nodules (n=7) and synovium (n=7) by interleukin 2 expansion, and subsequently characterised by flow cytometry for surface expression of αEβ7, α4β7, CD44, L selectin, LFA-1a, PECAM-1, and CD30.
RESULTS—(1) In rheumatoid nodules, the palisading layer strongly stains for ICAM-1 and PECAM-1, but less pronounced for CD44. VCAM-1 staining was usually negative. ICAM-1 is upregulated in the vessels surrounding the central zone of fibrinoid necrosis. The immunohistological picture in different nodules derived from the same patient was similar. (2) The endothelial expression of adhesion molecules is comparable in RA nodules and synovium on an individual level, except for E selectin, which is overexpressed in nodule endothelium. (3) T cell lines from nodules and synovium display similar adhesion molecule profiles. However, the expression of CD30, a T cell activation marker linked with Th2 subsets, is higher in nodules compared with synovium.
CONCLUSION—These data support a recirculation hypothesis of T cells between articular and extra-articular manifestations in RA, although the activation state of the T cells in each of these localisations may differ.
Keywords: T cells; adhesion molecules; rheumatoid nodules; rheumatoid synovium 相似文献
108.
Lu Zhang Eman A. Hamad Mélanie Vausort Hajime Funakoshi Arthur M. Feldman Daniel R. Wagner Yvan Devaux 《CTS Clinical and Translational Science》2015,8(2):100-106
Purpose
Long noncoding RNAs (lncRNAs) constitute an emerging group of noncoding RNAs, which regulate gene expression. Their role in cardiac disease is poorly known. Here, we investigated the association between lncRNAs and left ventricular hypertrophy.Methods
Wild‐type and adenosine A2A receptor overexpressing mice (A2A‐Tg) were subjected to transverse aortic constriction (TAC) and expression of lncRNAs in the heart was investigated using genome‐wide microarrays and an analytical pipeline specifically developed for lncRNAs.Results
Microarray analysis identified two lncRNAs up‐regulated and three down‐regulated in the hearts of A2A‐Tg mice subjected to TAC. Quantitative PCR showed that lncRNAs 2900055J20Rik and Gm14005 were decreased in A2A‐Tg mice (3.5‐ and 1.8‐fold, p < 0.01). We found from public microarray dataset that 2900055J20Rik and Gm14005 were increased in TAC mice compared to sham‐operated animals (1.8‐ and 1.4‐fold, after 28 days, p < 0.01). Interestingly, in this public dataset, cardioprotective drug JQ1 decreased 2900055J20Rik and Gm14005 expression by 2.2‐ and 1.6‐fold (p < 0.01).Conclusions
First, we have shown that data on lncRNAs can be obtained from gene expression microarrays. Second, expression of lncRNAs 2900055J20Rik and Gm14005 is regulated after TAC and can be modulated by cardioprotective molecules. These observations motivate further investigation of the therapeutic value of lncRNAs in the heart. 相似文献109.
黏附分子介导的细胞黏附是基本的生命现象 ,是细胞的生长及分化、炎症、血栓形成等一系列重要生理和病理过程的基础 ;扩张型心肌病一直是心血管领域的难点 ,其发病机制包括病毒的持续感染致心肌炎转化和自身免疫等。黏附分子在扩张型心肌病发生及发展中起着一定的重要作用 ,抗黏附治疗也成为扩张型心肌病防治的重要方面。 相似文献
110.