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首页> 外文期刊>Cell Biochemistry and Biophysics >Proinflammatory cytokines upregulate mRNA expression and secretion of vascular endothelial growth factor in cultured human airway smooth muscle cells
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Proinflammatory cytokines upregulate mRNA expression and secretion of vascular endothelial growth factor in cultured human airway smooth muscle cells

机译：促炎细胞因子上调人气道平滑肌细胞中mRNA的表达和血管内皮生长因子的分泌

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摘要

Airflow obstruction in chronic airway disease is associated with airway and pulmonary vascular remodeling, of which the molecular mechanisms are poorly understood. Paracrine actions of angiogenic factors released by resident or infiltrating inflammatory cells following activation by proinflammatory cytokines in diseased airways could play a major role in the airway vascular remodeling process. Here, the proinflammatory cytokines interleukin (IL)-1β, and tumor necrosis factor (TNF)-α were investigated on cell cultures of human airway smooth muscle (ASM) for their effects on mRNA induction and protein release of the angiogenic peptide, vascular endothelial growth factor (VEGF). IL-1β (0.5 ng/mL) and TNF-α (10ng/mL) each increased VEGF mRNA (3.9 and 1.7 kb) expression in human ASM cells, reaching maximal levels between 16 and 24 and 4 and 8h, respectively. Both cytokines also induced a time-dependent release of VEGF, which was not associated with increased ASM growth. Preincubation of cells with 1μM dexamethasone abolished enhanced release of VEGF by TNF-α. The data suggest that human ASM cells express and secrete VEGF in response to proinflammatory cytokines and may participate in paracrine inflammatory mechanisms of vascular remodeling in chronic airway disease.
机译：慢性气道疾病中的气流阻塞与气道和肺血管重塑有关，但对其分子机制了解甚少。在患病气道中由促炎细胞因子激活后，由常驻或浸润性炎症细胞释放的血管生成因子的旁分泌作用可能在气道血管重塑过程中发挥重要作用。在这里，在人气道平滑肌（ASM）的细胞培养物中研究了促炎细胞因子白介素（IL）-1β和肿瘤坏死因子（TNF）-α对血管生成肽，血管内皮蛋白的mRNA诱导和蛋白释放的影响生长因子（VEGF）。 IL-1β（0.5 ng / mL）和TNF-α（10ng / mL）分别增加人ASM细胞中VEGF mRNA（3.9和1.7 kb）的表达，分别达到16、24、4和8h的最高水平。两种细胞因子还诱导了VEGF的时间依赖性释放，这与ASM的增长无关。用1μM地塞米松预培养细胞可消除TNF-α增强的VEGF释放。数据表明，人ASM细胞响应促炎性细胞因子表达和分泌VEGF，并且可能参与慢性气道疾病中血管重塑的旁分泌炎症机制。

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  • 来源
    《Cell Biochemistry and Biophysics》 |2005年第1期|119-129|共11页
  • 作者

    V. K. T. Alagappan; S. McKay; A. Widyastuti; I. M. Garrelds; A. J. J. C. Bogers; H. C. Hoogsteden; S. J. Hirst; H. S. Sharma;

  • 作者单位

    Department of Pharmacology University Medical Center Rotterdam Dr. Molewaterplein 50 3015 GE Rotterdam The Netherland;

    Department of Pharmacology University Medical Center Rotterdam Dr. Molewaterplein 50 3015 GE Rotterdam The Netherland;

    Department of Pharmacology University Medical Center Rotterdam Dr. Molewaterplein 50 3015 GE Rotterdam The Netherland;

    Department of Pharmacology University Medical Center Rotterdam Dr. Molewaterplein 50 3015 GE Rotterdam The Netherland;

    Department of Cardiothoracic Surgery University Medical Center Rotterdam Dr. Molewaterplein 50 3015 GE Rotterdam The Netherland;

    Department of Pulmonary Medicine Erasmus MC University Medical Center Rotterdam Dr. Molewaterplein 50 3015 GE Rotterdam The Netherland;

    Asthma Allergy ampamp Respiratory Science The Guy''s King''s College ampamp St. Thomas'' School of Medicine King''s College London London UK;

    Department of Pharmacology University Medical Center Rotterdam Dr. Molewaterplein 50 3015 GE Rotterdam The Netherland;

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  • 正文语种 eng
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  • 关键词

    Cytokine; vascular endothelial growth factor; airway smooth muscle; enzymelinked immunosorbent assay; human;

    机译：细胞因子;血管内皮生长因子;气道平滑肌;酶联免疫吸附试验;人;

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