REGULATION OF GENE-EXPRESSION OF MACROPHAGE-COLONY STIMULATING FACTOR IN HUMAN FIBROBLASTS BY THE ACUTE PHASE RESPONSE MEDIATORS INTERLEUKIN (IL)-1-BETA, TUMOR-NECROSIS-FACTOR-ALPHA AND IL-6 (Retracted Article)
REGULATION OF GENE-EXPRESSION OF MACROPHAGE-COLONY STIMULATING FACTOR IN HUMAN FIBROBLASTS BY THE ACUTE PHASE RESPONSE MEDIATORS INTERLEUKIN (IL)-1-BETA, TUMOR-NECROSIS-FACTOR-ALPHA AND IL-6 (Retracted Article)
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DOI：
10.1016/0014-5793(91)80213-m
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发表时间：
1991-03-11
期刊：
影响因子：
3.5
通讯作者：
HERRMANN, F
中科院分区：
文献类型：
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作者：
MANTOVANI, L;HENSCHLER, R;HERRMANN, F
成纤维细胞构成骨髓基质的主要成分。它们通过提供细胞组织和组织凝聚所需的支架以及通过产生可溶性分子（包括集落刺激因子（CSF）和调节造血的各种白细胞介素）在血细胞发育中发挥关键作用。我们的数据表明，激活的单核细胞大量产生的急性时相反应介质白细胞介素（IL）-1 β，肿瘤坏死因子（TNF）-α和IL-6，通过转录和转录后机制增强成纤维细胞中巨噬细胞集落刺激因子（M-CSF）的水平。这些蛋白诱导M-CSF转录水平的作用依赖于新蛋白的合成，并且不受蛋白激酶C（PKC）刺激的介导，因为通过成纤维细胞长期暴露于佛波酯TPA而耗尽细胞PKC库并不能阻止因子诱导的M-CSF转录合成。然而，通过异喹啉磺酰胺衍生物H7阻断PKC并因此抑制磷酸化与成纤维细胞对TNF-α和IL-6的反应增强相关。
Fibroblasts constitute a major element of the bone marrow stroma. They play a pivotal role in blood cell development by providing the scaffolding required for cellular organization and tissue cohesion and by producing soluble molecules including colony stimulating factors (CSFs) and various interleukins regulating hematopoiesis. Our data demonstrate that the acute phase response mediators interleukin (IL)-1 beta, tumor necrosis factor (TNF)-alpha and IL-6 which are abundantly produced by activated monocytes, enhance levels of macrophage-colony stimulating factor (M-CSF) in fibroblasts by both transcriptional and post-transcriptional mechanisms. The action of these proteins to induce M-CSF transcript levels was dependent on synthesis of new proteins and was not mediated by protein kinase C (PKC) stimulation as depletion of cellular PKC pools by prolonged exposure of fibroblasts to phorbolester TPA did not prevent factor induced synthesis of M-CSF transcripts. However, blockade of PKC by the isoquinoline sulfonamide derivative H7 and thus inhibition of phosphorylation was associated with augmentation of the fibroblasts response to TNF-alpha and IL-6.