Expression of colony-stimulating factor genes by normal human mesothelial cells and human malignant mesothelioma cells lines in vitro.
Expression of colony-stimulating factor genes by normal human mesothelial cells and human malignant mesothelioma cells lines in vitro.
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DOI：
10.1182/blood.v74.3.940.bloodjournal743940
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发表时间：
1989-08
期刊：
影响因子：
20.3
通讯作者：
G. Demetri;Beatrice W. Zenzie;J. Rheinwald;J. Griffin
中科院分区：
文献类型：
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作者：
G. Demetri;Beatrice W. Zenzie;J. Rheinwald;J. Griffin
我们研究了正常人间皮瘤细胞和人恶性间皮瘤细胞系在培养中产生造血集落刺激因子（CSF）的能力。正常二倍体人间皮细胞的早期传代培养物自发表达可检测水平的M-CSF mRNA转录物，但缺乏可检测的GM-CSF或G-CSF转录物。正常间皮细胞暴露于表皮生长因子（EGF）、脂多糖（LPS）或肿瘤坏死因子（TNF）诱导G-CSF mRNA表达。EGF和TNF的组合诱导的G-CSF转录比单独使用任何一种因子多三倍。GM-CSF转录物仅由TNF和EGF的组合诱导。白细胞介素-1 β（IL-1 β）转录物可被EGF、TNF或LPS诱导，并被氢化可的松（HC）抑制。所有检测的恶性间皮瘤细胞系也自发表达M-CSF转录本。然而，与正常间皮瘤细胞相反，四种恶性间皮瘤细胞系中的两种也在没有TNF、EGF或LPS刺激的情况下自主表达G-CSF和GM-CSF转录物。生物活性CSF的分泌通过测试由所检查的各种细胞类型调节的培养基来证实。通过北方分析，生物活性CSF的检测与可检测CSF转录物的存在相关性良好。这些数据表明：（a）正常人间皮瘤细胞在培养物中自发表达可检测水平的M-CSF mRNA;（B）EGF是最佳诱导G-CSF和GM-CSF表达的必需辅因子;（c）正常间皮瘤细胞暴露于炎性介质如LPS和TNF增加CSF和IL-1 β的转录物水平;和（d）与正常的人间皮瘤细胞相比，人恶性间皮瘤的一些细胞系表现出多种细胞因子（包括G-CSF、GM-CSF、IL-1 β和IL-6）的异常基因表达。
We investigated normal human mesothelial cells and human malignant mesothelioma cell lines for the ability to produce hematopoietic colony-stimulating factors (CSFs) in culture. Early passage cultures of normal diploid human mesothelial cells spontaneously expressed detectable levels of M-CSF mRNA transcripts, but lacked detectable transcripts for GM-CSF or G-CSF. Exposure of normal mesothelial cells to epidermal growth factor (EGF), lipopolysaccharide (LPS), or tumor necrosis factor (TNF) induced expression of G-CSF mRNA. The combination of EGF and TNF induced threefold more G-CSF transcripts than did either factor alone. GM-CSF transcripts were induced only by the combination of TNF and EGF. Interleukin-1 beta (IL-1 beta) transcripts were induced by EGF, TNF, or LPS and were inhibited by hydrocortisone (HC). All malignant mesothelioma cell lines tested also spontaneously expressed M-CSF transcripts. However, in contrast to normal mesothelial cells, two of four malignant mesothelioma cell lines also autonomously expressed G-CSF and GM-CSF transcripts without TNF, EGF, or LPS stimulation. Secretion of biologically active CSFs was confirmed by testing media conditioned by the various cell types examined. The detection of biologically active CSFs correlated well with the presence of detectable CSF transcripts by Northern analysis. These data indicate that (a) normal human mesothelial cells spontaneously express detectable levels of M-CSF mRNA in culture; (b) EGF is an essential cofactor for optimal induction of G-CSF and GM-CSF expression; (c) exposure of normal mesothelial cells to inflammatory mediators such as LPS and TNF increases the levels of transcripts for CSFs and IL-1 beta; and (d) as compared with normal human mesothelial cells, some cell lines of human malignant mesothelioma exhibit aberrant gene expression for multiple cytokines, including G-CSF, GM-CSF, IL-1 beta, and IL-6.