Mechanisms of GM-CSF increase by diesel exhaust particles in human airway epithelial cells
Mechanisms of GM-CSF increase by diesel exhaust particles in human airway epithelial cells
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DOI：
10.1152/ajplung.2000.278.1.l25
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发表时间：
2000-01-01
影响因子：
4.9
通讯作者：
Marano, F
中科院分区：
文献类型：
--
作者：
Boland, S;Bonvallot, V;Marano, F
柴油机尾气颗粒增加人呼吸道上皮细胞中 GM-CSF 的机制。是。 J.生理学。肺细胞。梅尔.生理学。 278：L25-L32，2000。-我们之前已经证明，接触柴油机尾气颗粒 (DEP) 会刺激人气道上皮细胞分泌炎症细胞因子白细胞介素 8、白细胞介素 1 β 和粒细胞巨噬细胞集落刺激因子 (GM-CSF)，这些细胞因子与过敏性疾病有关。在本文中，我们使用人支气管上皮细胞系 16HBE14o- 研究了 DEP 引起 GM-CSF 释放增加的机制。 RT-PCR 分析显示 DEP 处理后 GM-CSF mRNA 水平增加。比较 DEP、提取的 DEP 或 DEP 提取物的效果表明，GM-CSF 释放的增加主要是由于吸附的有机化合物，而不是由于 DEP 表面存在的金属，因为金属螯合剂去铁胺没有抑制作用。此外，自由基清除剂抑制 DEP 诱导的 GM-CSF 释放，表明活性氧参与了该反应。此外，金雀异黄素（一种酪氨酸激酶抑制剂）消除了 DEP 对 GM-CSF 释放的影响，而蛋白激酶 (PK) C、PKA、环氧合酶或脂氧合酶抑制剂则没有影响。 PD-98059（一种丝裂原激活蛋白激酶抑制剂）减弱了 DEP 的作用，而 SB-203580（一种 p38 丝裂原激活蛋白激酶抑制剂）的作用较低，而 DEP 确实增加了细胞外信号调节激酶的活性磷酸化形式，如蛋白质印迹所示。此外，抑制DEP吞噬作用的细胞松弛素D可减少DEP处理后GM-CSF释放的增加。总之，这些数据表明 GM-CSF 释放的增加主要是由于吸附的有机化合物，并且天然 DEP 的作用需要颗粒的内吞作用。活性氧和酪氨酸激酶可能参与 DEP 触发的 GM-CSF 反应信号传导。
Mechanisms of GM-CSF increase by diesel exhaust particles in human airway epithelial cells. Am. J. Physiol. Lung Cell. Mel. Physiol. 278: L25-L32, 2000.-We have previously shown that exposure to diesel exhaust particles (DEPs) stimulates human airway epithelial cells to secrete the inflammatory cytokines interleukin-8, interleukin-1 beta, and granulocyte-macrophage colony-stimulating factor (GM-CSF) involved in allergic diseases. In the present paper, we studied the mechanisms underlying the increase in GM-CSF release elicited by DEPs using the human bronchial epithelial cell line 16HBE14o-. RT-PCR analysis has shown an increase in GM-CSF mRNA levels after DEP treatments. Comparison of the effects of DEPs, extracted DEPs, or extracts of DEPs has shown that the increase in GM-CSF release is mainly due to the adsorbed organic compounds and not to the metals present on the DEP surface because the metal chelator desferrioxamine had no inhibitory effect. Furthermore, radical scavengers inhibited the DEP-induced GM-CSF release, showing involvement of reactive oxygen species in this response. Moreover genistein, a tyrosine kinase inhibitor, abrogated the effects of DEPs on GM-CSF release, whereas protein kinase (PK) C, PKA, cyclooxygenase, or lipoxygenase inhibitors had no effect. PD-98059, an inhibitor of mitogen-activated protein kinase, diminished the effects of DEPs, whereas SB-203580, an inhibitor of p38 mitogen-activated protein kinase, had a lower effect, and DEPs did actually increase the active, phosphorylated form of the extracellular signal-regulated kinase as shown by Western blotting. In addition, cytochalasin D, which inhibits the phagocytosis of DEPs, reduced the increase in GM-CSF release after DEP treatment. Together, these data suggest that the increase in GM-CSF release is mainly due to the adsorbed organic compounds and that the effect of native DEPs requires endocytosis of the particles. Reactive oxygen species and tyrosine kinase(s) may be involved in the DEP-triggered signaling of the GM-CSF response.