Reactive oxygen and nitrogen intermediates increase transforming growth factor-beta1 release from human epithelial alveolar cells through two different mechanisms.

Reactive oxygen and nitrogen intermediates increase transforming growth factor-beta1 release from human epithelial alveolar cells through two different mechanisms.
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活性氧和氮中间体通过两种不同的机制增加人上皮肺泡细胞的转化生长因子-β1 释放。

DOI:
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发表时间:
1999
影响因子:
6.4
通讯作者:
L. Baud
L. Baud
中科院分区:
医学1区
文献类型:
--
作者:
A. Bellocq;E. Azoulay;S. Marullo;Antoine Flahault;B. Fouqueray;C. Philippe;Jacques Cadranel;L. Baud

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转化生长因子 (TGF)-β1 是一种参与炎症过程后的肺修复和纤维化机制的生长因子。我们试图研究炎症细胞产生活性氧中间体(ROI)或活性氮中间体(RNI)与肺泡上皮细胞表达 TGF-β1 之间的联系。通过特定的酶联免疫吸附测定,将 A549 肺上皮细胞系暴露于 ROI 生成系统(黄嘌呤和黄嘌呤氧化酶)或 RNI 供体(S-亚硝基-N-乙酰基青霉胺 [SNAP]),促进 TGF-β1 释放呈时间和剂量依赖性增加。在峰值时,TGF-β1 的水平是对照值的两倍。 ROI 诱导的 TGF-β1 释放被过氧化氢酶减弱,并且不受超氧化物歧化酶的影响,表明过氧化氢的参与。该反应也被 5, 6-二氯-1-β-D-呋喃核糖基苯并咪唑 (DRB)(一种特定的 RNA 聚合酶 II 抑制剂)减弱,并伴随着 TGF-β1 信使 RNA 的相应增加(通过定量/竞争性逆转录聚合酶链反应测量),表明转录机制和可能的其他下游机制的参与。相比之下,RNI 诱导的 TGF-β1 释放不受 DRB 影响,并被蛋白质合成抑制剂放线菌酮减弱,表明涉及翻译和翻译后机制。这种反应需要环磷酸鸟苷 (cGMP) 介导的过程,因为 (1) 免疫反应性 cGMP 在 SNAP 处理的细胞的培养基中积累; (2) SNAP 诱导的 TGF-β1 释放被 KT 5823(一种 cGMP 依赖性蛋白激酶抑制剂)减弱; (3)通过将细胞暴露于可渗透膜的二丁酰-cGMP或心房钠尿因子(一种已知的颗粒鸟苷酸环化酶激动剂),TGF-β1释放也得到类似的增加。这些数据表明,人肺泡上皮细胞体外暴露于 ROI 和 RNI 可通过不同机制增​​强 TGF-β1 的释放。在体内,这种控制可能构成炎症和纤维化过程之间的分子联系。
Transforming growth factor (TGF)-beta1 is a growth factor involved in the mechanisms of lung repair and fibrosis that follow inflammatory processes. We sought to examine the link between the generation of reactive oxygen intermediates (ROI) or reactive nitrogen intermediates (RNI) by inflammatory cells and the expression of TGF-beta1 by alveolar epithelial cells. Exposure of the A549 lung epithelial cell line to either an ROI generating system (xanthine and xanthine oxidase) or an RNI donor (S-nitroso-N-acetyl-penicillamine [SNAP]) promoted a time- and dose-dependent increase in TGF-beta1 release, as measured by a specific enzyme-linked immunosorbent assay. At the peak, the levels of TGF-beta1 were twice the control values. The induction of TGF-beta1 release by ROI was blunted by catalase and unaffected by superoxide dismutase, indicating the involvement of hydrogen peroxide. The response was also blunted by 5, 6-dichloro-1-beta-D-ribofuranosyl benzimidazole (DRB), a specific RNA polymerase II inhibitor, and accompanied by a corresponding increase in TGF-beta1 messenger RNA, as measured by quantitative/competitive reverse transcription polymerase chain reaction, suggesting the involvement of transcriptional mechanisms and possibly other downstream mechanisms. In contrast, RNI-induced TGF-beta1 release was unaffected by DRB and blunted by the protein synthesis inhibitor cycloheximide, suggesting the involvement of translational and post-translational mechanisms. This response required cyclic guanosine monophosphate (cGMP)- mediated processes because (1) immunoreactive cGMP accumulated in the culture medium of SNAP-treated cells; (2) SNAP-induced TGF-beta1 release was blunted by KT 5823, an inhibitor of cGMP-dependent protein kinase; and (3) similar increase in TGF-beta1 release was obtained by cell exposure to membrane-permeable dibutyryl-cGMP or to atrial natriuretic factor, a known agonist of particulate guanylate cyclase. These data suggest that in vitro exposure of human alveolar epithelial cells to ROI and RNI enhances TGF-beta1 release through different mechanisms. In vivo, this control may constitute a molecular link between inflammatory and fibrotic processes.
DOI: 10.1016/0006-2952(91)90296-h
发表时间: 1991-08
影响因子: 5.8
作者:
Q. Wang;S. Giri;D. Hyde;C. Li
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DOI: --
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氧化停滞的肺泡上皮细胞中的胰岛素样生长因子、其结合蛋白和转化生长因子-β1。
DOI: --
发表时间: 1994
期刊: The Journal of biological chemistry
影响因子: --
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