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首页> 外文期刊>Cytokine >Tumour necrosis factor alpha enhances the expression of hydroxyl lyase, cytoplasmic antiproteinase-2 and a dual specificity kinase TTK in human chondrocyte-like cells.
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Tumour necrosis factor alpha enhances the expression of hydroxyl lyase, cytoplasmic antiproteinase-2 and a dual specificity kinase TTK in human chondrocyte-like cells.

机译:肿瘤坏死因子α增强了人类软骨样细胞中羟裂合酶,胞质抗蛋白酶-2和双重特异性激酶TTK的表达。

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摘要

Tumour necrosis factor alpha (TNF-alpha) is a cytokine with pleiotropic effects on cells ranging from proliferation to apoptosis. These biological effects of TNF-alpha are believed to be elicited by the induction or enhancement of the expression of TNF-alpha responsive genes in the target cells. TNF-alpha is pro-inflammatory and a principal mediator in the pathogenesis of arthritis. The activation of an inflammatory cascade by TNF-alpha in arthritis results in the degradation of cartilage, joint destruction and loss of function. Because TNF-alpha is an important mediator in the pathogenesis of arthritis, the present study addresses the identification of novel TNF-alpha responsive genes in HTB-94 cell line which is of human origin and maintains a chondrocytic phenotype. The three identified cDNAs were previously not known to be induced or upregulated by TNF-alpha in chondrocytes or cells of chondrocytic lineage. One of the identified cDNAs had sequence similarity to human hydroxyl lyase mRNA (PLOD), an enzyme involved in collagen biosynthesis and its metabolism; the second cDNA had sequence similarity to the human cytoplasmic anti-proteinase-2 mRNA (CAP-2), a member of a group of proteins shown to be associated with protecting cells from TNF-alpha-induced apoptosis; and the third cDNA had sequence similarity to a dual specificity kinase, TTK, which is associated with cell proliferation. Relative gene expression level analysis by PCR and by Northern blotting revealed that treatment with TNF-alpha enhanced the expression of PLOD, CAP2 and TTK transcripts which confirmed the results obtained with display gels. Furthermore, TTK mRNA expression was also induced in human articular chondrocytes treated with TNF-alpha but not in untreated chondrocytes. Our results suggest that these genes may play a role in chondrocytic responses to TNF-alpha-mediated stimuli affecting the cartilage homeostasis. Copyright 2000 Academic Press.
机译:肿瘤坏死因子α(TNF-alpha)是一种细胞因子,对细胞具有多效作用,范围从增殖到凋亡。据信TNF-α的这些生物学效应是通过诱导或增强靶细胞中TNF-α响应基因的表达而引起的。 TNF-α是促炎性的,是关节炎发病机理的主要介质。 TNF-α在关节炎中激活炎症级联反应会导致软骨退化,关节破坏和功能丧失。由于TNF-α是关节炎发病机制中的重要介体,因此本研究致力于鉴定人类起源的HTB-94细胞系中新的TNF-α响应基因,并维持软骨细胞表型。在软骨细胞或软骨细胞谱系细胞中,先前尚不知道这三种已鉴定的cDNA是由TNF-α诱导或上调的。鉴定出的一种cDNA与人类羟裂合酶mRNA(PLOD)具有序列相似性,后者是一种参与胶原生物合成及其代谢的酶。第二个cDNA与人类细胞质抗蛋白酶2 mRNA(CAP-2)具有序列相似性,CAP-2是一组蛋白质的成员,被证明与保护细胞免受TNF-α诱导的细胞凋亡有关。第三个cDNA与双重特异性激酶TTK具有序列相似性,TTK与细胞增殖有关。通过PCR和Northern印迹的相对基因表达水平分析显示,用TNF-α处理增强了PLOD,CAP2和TTK转录物的表达,这证实了用展示凝胶获得的结果。此外,在用TNF-α处理的人关节软骨细胞中也诱导了TTK mRNA表达,但在未处理的软骨细胞中未诱导。我们的结果表明,这些基因可能在对TNF-α介导的刺激软骨稳态的软骨反应中起作用。版权所有2000学术出版社。

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