Stimulus- and cell-type-specific regulation of CCAAT-enhancer binding protein isoforms in glomerular mesangial cells by lipopolysaccharide and cytokines
Stimulus- and cell-type-specific regulation of CCAAT-enhancer binding protein isoforms in glomerular mesangial cells by lipopolysaccharide and cytokines
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DOI：
10.1016/s0925-4439(00)00016-8
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发表时间：
2000-06-15
影响因子：
6.2
通讯作者：
Ramji, DP
中科院分区：
文献类型：
--
作者：
Granger, RL;Hughes, TR;Ramji, DP
CCAAT 增强子结合蛋白 (C/EBP) 家族的结合位点存在于已知在肾小球炎症性疾病发病过程中由系膜细胞 (MC) 表达的几个基因的启动子区域中。然而，人们对已知激活 MC 的药物对 C/EBP 家族的精确调节知之甚少。我们在此报告了白介素-1 (IL)-1 以及脂多糖 (LPS)、血小板源性生长因子 (PDGF)、IL-6、干扰素-γ (IFN-γ) 和肿瘤坏死因子-α (TNF-α) 对原代大鼠 MC 中 C/EBP 表达谱和功能性 DNA 结合活性的作用。确定了 C/EBP mRNA 表达和 DNA 结合活性的细胞类型和刺激特异性调节，其中 C/EBP α 由 LPS 诱导，C/EBP β 由 LPS、IL-1、TNF-α 诱导，C/EBP δ 由 LPS、IL-1、IFN-γ、TNF-α 和 PDGF 诱导。这种差异调节，特别是 C/EBP β 的调节，可能是 MC 中 C/EBP 调节基因表达的介质特异性差异的原因。此外，还确定了 C/EBP δ 调节中潜在的转录后机制的参与。这些研究为肾脏疾病期间基因表达的刺激特异性调节提供了新的见解。 (C) 2000 Elsevier Science B.V. 保留所有权利。
Binding sites for the CCAAT-enhancer binding protein (C/EBP) family are present in the promoter regions of several genes that are known to be expressed by mesangial cells (MC) during the pathogenesis of glomerular inflammatory diseases. The precise regulation of the C/EBP family by agents that are known to activate MC is, however, poorly understood. We report here the action of interleukin-1 (IL)-1 and, for the first time, lipopolysaccharide (LPS), platelet-derived growth factor (PDGF), IL-6, interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha) on the C/EBP expression profile and functional DNA binding activity in primary rat MC. Both cell-type- and stimulus-specific regulation of C/EBP mRNA expression and DNA binding activity were identified, with C/EBP alpha being induced by LPS, C/EBP beta by LPS, IL-1, TNF-alpha and C/EBP delta by LPS, IL-1, IFN-gamma, TNF-alpha and PDGF. Such differential regulation, particularly that of C/EBP beta, may be responsible for the mediator-specific differences in the expression of C/EBP-regulated genes in MC. Additionally, the involvement of potential post-transcriptional mechanisms in the regulation of C/EBP delta were identified. These studies provide novel insights into the stimulus-specific regulation of gene expression during renal diseases. (C) 2000 Elsevier Science B.V. All rights reserved.