首页> 外文会议>2007 summer computer simulation conference (SCSC'07) >MICROARRAY ANALYSIS REVEALS CC CHEMOKINE CCL-1 RESPONSIVE GENE EXPRESSION IN HUMAN HELA CELLS
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MICROARRAY ANALYSIS REVEALS CC CHEMOKINE CCL-1 RESPONSIVE GENE EXPRESSION IN HUMAN HELA CELLS

机译:微阵列分析揭示CC趋化因子CCL-1在人类Hela细胞中的反应性基因表达

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Human CC chemokine, CCL-1 is a chemotactic cytokinernimplicated in a variety of biological responses, namelyrninflammation and chemotaxis, in many cell types. We havernpreviously shown that the CC chemokine, CCL-1 and itsrnreceptor CCR8 are expressed and causes migration ofrncancer cells: skin, melanoma, MDMA (breast cancer) andrnKaposi's sarcoma spindle cells. In the present study wernexamined the role of CCL-1 and its receptor CCR8 in thernregulation of gene expression by microarray analysis andrntargeted siRNA inhibition in human cervical carcinomarn(HeLa ) cells.rnWe have found that HeLa cells constitutively express CCR8rnand this expression of CCR8 is stimulated by CCL-1.rnInorder to understand the underlying mechanisms wernlooked at gene expression during CCL1 and CCR8 mediatedrninteractions. Affymetrix human microarray data analysisrnrevealed that CCL-1 regulates genes that are involved inrnangiogenesis, apoptosis, oxidative stress and chemotaxis.rnCC chemokine CCL-2 (MCP-1) a potent regulator ofrnmonocyte/macrophage chemotaxis and invasion in variousrndisease states is induced in response to CCL1. Thisrnstimulation of CCL-2 by CCL-1 was further validated byrnRT-PCR analysis. In corollary, targeted CCR8 siRNArninhibition down regulated CCL-2 expression furtherrnsubstantiating our findings. It is known that CCL2 protectsrnhuman neuronal cells from tat-induced apoptosis and CCL1rnis anti-apoptotic for thymic and leukemia cells. In thernpresent study genes involved in oxidative stress arerninhibited and those involved in protection against apoptosisrnare upregulated suggesting a common pathway for the twornCC chemokines. Close examination of the role of CCL-rn1/CCR8 pathway in the regulation of CCL-2 and otherrnangiogenic and/or apoptotic factors will provide importantrninsights into vascular cell pathologies.
机译:人CC趋化因子CCL-1是一种趋化性细胞因子,涉及许多细胞类型的多种生物学反应,即炎症和趋化性。先前我们已经证明CC趋化因子,CCL-1及其受体CCR8被表达并引起癌细胞的迁移:皮肤,黑色素瘤,MDMA(乳腺癌)和卡波西氏肉瘤梭形细胞。本研究通过芯片分析和靶向siRNA抑制人宫颈癌(HeLa)细胞中CCL-1及其受体CCR8在基因表达调控中的作用。我们发现HeLa细胞组成性表达CCR8rn,并刺激了CCR8的这种表达。为了了解在CCL1和CCR8介导的相互作用过程中基因表达的基本机制,我们采用了CCL-1.rn。 Affymetrix人类微阵列数据分析表明,CCL-1调节涉及血管生成,凋亡,氧化应激和趋化性的基因.rnCC趋化因子CCL-2(MCP-1)是对核糖细胞/巨噬细胞趋化性和各种疾病状态的侵袭的有效调节剂。 CCL1。通过RT-PCR分析进一步证实了CCL-1对CCL-2的刺激。结果,靶向CCR8 siRNA抑制下调了CCL-2表达,进一步证实了我们的发现。众所周知,CCL2保护人类神经元细胞免受tat诱导的细胞凋亡以及CCL1rnis对胸腺和白血病细胞的抗凋亡作用。在目前的研究中,与氧化应激有关的基因被抑制,而与针对凋亡的保护有关的基因被上调,暗示了这两种CC趋化因子的共同途径。仔细检查CCL-rn1 / CCR8通路在CCL-2和其他血管生成和/或凋亡因子调控中的作用将为了解血管细胞病理学提供重要的依据。

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