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首页> 外文期刊>Cellular immunology >alphaVbeta3-integrin expression through ERK activation mediates cell attachment and is necessary for production of tumor necrosis factor alpha in monocytic THP-1 cells stimulated by phorbol myristate acetate.
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alphaVbeta3-integrin expression through ERK activation mediates cell attachment and is necessary for production of tumor necrosis factor alpha in monocytic THP-1 cells stimulated by phorbol myristate acetate.

机译:通过ERK激活的alphaVbeta3-整联蛋白表达介导细胞附着,是佛波肉豆蔻酸酯乙酸酯刺激的单核THP-1细胞中肿瘤坏死因子α的产生所必需的。

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摘要

Macrophages play a key role in inflammation. Activated macrophages express adhesion molecules and produce tumor necrosis factor alpha (TNFalpha). Integrins are the main adhesion molecules that mediate binding to the extracellular matrix and they are involved in intracellular pathways. In the present study, human monocytic THP-1 cell adhesion to uncoated plastic plate was examined to investigate the regulatory mechanism of TNFalpha secretion. Addition of phorbol myristate acetate (PMA) for THP-1 cell activation induced cell adhesion in parallel with TNFalpha production. Among the mitogen-activated protein kinase pathways, the protein kinase C (PKC)-extracellular signal-regulated kinase (ERK) pathway was involved in alphaVbeta3-integrin expression and PMA-induced cell adhesion. Flow cytometry and reverse transcription - quantitative polymerase chain reaction analysis revealed increased expression of matrix-binding integrins including integrin-alphaVbeta3. Blockade of alphaVbeta3-integrin by a specific antibody suppressed cell adhesion and TNFalpha production. These findings indicate that TNFalpha production from THP-1 cells is PKC-ERK, alphaVbeta3-integrin and adhesion-dependent and its related pathway could be a target for TNFalpha-related diseases.
机译:巨噬细胞在炎症中起关键作用。活化的巨噬细胞表达粘附分子并产生肿瘤坏死因子α(TNFalpha)。整联蛋白是介导与细胞外基质结合的主要粘附分子,它们参与细胞内途径。在本研究中,检查了人类单核细胞THP-1细胞对未包被的塑料板的粘附力,以研究TNFα分泌的调节机制。为THP-1细胞激活添加佛波肉豆蔻酸酯乙酸酯(PMA)会与TNFα产生同时引起细胞粘附。在有丝分裂原激活的蛋白激酶途径中,蛋白激酶C(PKC)-细胞外信号调节激酶(ERK)途径与alphaVbeta3整合素表达和PMA诱导的细胞粘附有关。流式细胞仪和逆转录-定量聚合酶链反应分析显示,包括整联蛋白-αVbeta3的基质结合整联蛋白表达增加。特异性抗体对alphaVbeta3-integrin的阻滞抑制了细胞粘附和TNFalpha的产生。这些发现表明,THP-1细胞的TNFα产生是PKC-ERK,αVbeta3-整联蛋白且依赖粘附,其相关途径可能是TNFα相关疾病的靶标。

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