Induction of early growth response-1 gene by interleukin-1 beta and tumor necrosis factor-alpha in normal human bone marrow stromal an osteoblastic cells: regulation by a protein kinase C inhibitor.
Induction of early growth response-1 gene by interleukin-1 beta and tumor necrosis factor-alpha in normal human bone marrow stromal an osteoblastic cells: regulation by a protein kinase C inhibitor.
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正常人骨髓基质和成骨细胞中白细胞介素 1 β 和肿瘤坏死因子 α 诱导早期生长反应 1 基因：蛋白激酶 C 抑制剂的调节。
DOI：
10.1007/bf00239321
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发表时间：
1996
影响因子：
4.3
通讯作者：
Avioli,LV
中科院分区：
文献类型：
--
作者：
Chaudhary,LR;Cheng,SL;Avioli,LV
早期生长反应-1 （Egr-1）基因被认为是一种核转录因子，参与成骨细胞的生长和分化调控。在本研究中，我们研究了白细胞介素-1 β (IL-β)和肿瘤坏死因子-α (TNF-α)是否在正常人骨髓基质（HBMS）和成骨细胞（HOB）中表达和诱导Egr-1 mRNA。结果表明，IL-1 β和TNF-α诱导Egr-1 mRNA的基础表达极低，且呈时间和剂量依赖性。Egr-1 mRNA的诱导在15分钟内检测到，60分钟达到最大，120分钟后下降到基础水平。IL-1β和TNF-α对Egr-1 mRNA的诱导被H-7完全抑制，提示有蛋白激酶c的介导作用。IL-1β和TNF-α对Egr-1 mRNA的诱导与从头蛋白合成无关，因为在蛋白合成抑制剂环己亚胺的存在下也能观察到这种诱导。胎牛血清和环己亚胺也能独立诱导Egr-1 mRNA表达。放线菌素D实验表明Egr-1 mRNA降解非常迅速，半衰期为30 min。我们的研究结果证实了Egr-1基因的表达以及IL-1β和TNF-α在原代培养的正常人骨髓基质（成骨细胞）和成骨细胞中的诱导作用。数据还显示，蛋白激酶C抑制剂H-7可抑制Egr-1基因的表达，提示IL-1 β和TNF-α诱导立即早期Egr-1基因的第一个直接早期步骤是激活蛋白激酶C或其他蛋白激酶导致特定转录因子的磷酸化。结果还表明，Egr-1是正常人成骨细胞中IL-1 β和TNF-α作用的重要介质。
The early growth response-1 (Egr-1) gene has been identified as a nuclear transcriptional factor and implicated in the regulation of growth and differentiation of osteoblastic cells. In the present study, we investigated whether Egr-1 mRNA is expressed and induced by interleukin-1 β (IL-β) and tumor necrosis factor-α (TNF-α) in normal human bond marrow stromal (HBMS) and osteoblastic (HOB) cells. Results demonstrate a very low basal expression of Egr-1 mRNA which is induced by IL-1 β and TNF-α in a time- and dose-dependent manner. Egr-1 mRNA induction was detectable within 15 min, reached maximal by 60 min and thereafter declined to basal levels by 120 min. Induction of Egr-1 mRNA by IL-1β and TNF-α was completely inhibited by H-7 suggesting the mediation of protein kinase C. The induction by IL-1 β and TNF-α of Egr-1 mRNA was independent of de novo protein synthesis since this induction was also observed in the presence of protein synthesis inhibitor cycloheximide. Fetal bovine serum and cycloheximide also independently induced the Egr-1 mRNA. Actinomycin D experiments demonstrated that Egr-1 mRNA is degraded very rapidly with a half-life of 30 min. Our results demonstrate the expression of Egr-1 gene and its induction by IL-1β, and TNF-α in normal human bone marrow stromal (osteoprogenitor) and osteoblastic cells in primary cultures. Data also reveal that the expression of Egr-1 gene is inhibited by protein kinase C inhibitor H-7 suggesting that the activation of protein kinase C or other protein kinases resulting in the phosphorylation of specific transcription factor(s) is the first immediate early step in the induction of immediate-early Egr-1 gene by IL-1 β and TNF-α. Results also suggest that Egr-1 is an important mediator of IL-1 β and TNF-α action in normal human osteoblastic cells.