Dexamethasone-induced increase in platelet-derived growth factor (B) mRNA in human alveolar macrophages and myelomonocytic HL60 macrophage-like cells.

Dexamethasone-induced increase in platelet-derived growth factor (B) mRNA in human alveolar macrophages and myelomonocytic HL60 macrophage-like cells.
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地塞米松诱导人肺泡巨噬细胞和骨髓单核 HL60 巨噬细胞样细胞中血小板衍生生长因子 (B) mRNA 的增加。

DOI:
10.1165/ajrcmb/7.2.198
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发表时间:
1992
影响因子:
6.4
通讯作者:
R. Shaw
R. Shaw
中科院分区:
医学1区
文献类型:
--
作者:
A. Haynes;R. Shaw

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来自肺泡巨噬细胞的血小板源性生长因子(B)(PDGF(B))被认为在协调纤维化反应中发挥核心作用。由于皮质类固醇广泛用于肺纤维化患者的治疗,我们询问皮质类固醇是否调节巨噬细胞中PDGF(B)基因的激活。吸烟者肺泡巨噬细胞PDGF(B)mRNA在地塞米松(P <0.05)、干扰素-γ(P <0.05)或两者联合(P <0.05)作用下表达增加。地塞米松没有改变编码转化生长因子-β(TGF-β)的mRNA的丰度,但降低了早期生长反应基因2(EGR 2)的mRNA。这些最初的实验需要大量的细胞,因此在吸烟者的巨噬细胞上进行。采用逆转录聚合酶链反应(RT-PCR)检测了健康非吸烟志愿者巨噬细胞中PDGF(B)mRNA的丰度。地塞米松单独刺激(P <0.05)或与IFN-γ联合刺激(P <0.05)后,不吸烟者巨噬细胞PDGF(B)mRNA表达增加。为了提供足够的细胞数量的动力学和剂量反应研究,在体外模型的佛波酯(TPA)诱导分化的HL 60细胞巨噬细胞样细胞。在这些细胞中,地塞米松导致PDGF(B)mRNA丰度增加20倍,这是浓度和时间依赖性的,但与TGF-β或EGFR 2 mRNA的变化无关。这项研究表明,除了它们的抗炎作用,皮质类固醇还可以增加PDGF(B)mRNA的丰度。
Platelet-derived growth factor (B) (PDGF(B)) from alveolar macrophages is thought to play a central role in orchestrating the fibrotic response. Because corticosteroids are widely used in the treatment of patients with lung fibrosis, we asked whether corticosteroids modulated PDGF(B) gene activation in macrophages. PDGF(B) mRNA in alveolar macrophages obtained from smokers was increased after culture in the presence of dexamethasone (P less than 0.05), interferon-gamma (IFN-gamma) (P less than 0.05), or both in combination (P less than 0.05). Dexamethasone did not alter the abundance of mRNA encoding transforming growth factor-beta (TGF-beta), but did decrease the mRNA of early growth response gene 2 (EGR2). These initial experiments required large numbers of cells and thus were performed on macrophages from smokers. The results were reproduced when PDGF(B) mRNA abundance in macrophages from healthy nonsmoking volunteers was measured by the reverse-transcriptase polymerase chain reaction (RT-PCR). There was an increase in PDGF(B) mRNA in macrophages from nonsmokers after stimulation with dexamethasone alone (P less than 0.05) or in combination with IFN-gamma (P less than 0.05). To provide adequate cell numbers for kinetic and dose-response studies, the in vitro model of phorbol ester (TPA)-induced differentiation of HL60 cells to macrophage-like cells was used. In these cells, dexamethasone caused a 20-fold increase in the abundance of PDGF(B) mRNA, which was concentration and time dependent but not associated with changes in TGF-beta or EGR2 mRNA. This study suggests that in addition to their anti-inflammatory effects, corticosteroids may also increase the abundance of PDGF(B) mRNA.
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发表时间: 1989-06
影响因子: --
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期刊: The Journal of biological chemistry
影响因子: --
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DOI: --
发表时间: 1990
期刊: The American review of respiratory disease
影响因子: --
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