Expression of transcription factor zinc-binding protein-89 (ZBP-89) is inhibited by inflammatory cytokines.
Expression of transcription factor zinc-binding protein-89 (ZBP-89) is inhibited by inflammatory cytokines.
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DOI：
10.2147/plmi.s6249
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发表时间：
2009-08-01
影响因子：
0.2
通讯作者：
Chambers M
中科院分区：
文献类型：
--
作者：
Borghaei RC;Chambers M
锌结合蛋白-89 (ZBP-89; ZNF148, BERF-1, BFCOL-1) 是 Kruppel 家族的锌指转录因子。它已被证明可以调节许多基因的表达，根据具体情况充当基因表达的激活剂或抑制剂。它在多种癌症中过度表达，但已被证明参与细胞凋亡，并部分通过与 p53 相互作用对细胞生长产生负面影响。此前，ZBP-89 被证明可以通过与核因子 κB (NF-κB) 竞争的多态性启动子元件结合来激活基质金属蛋白酶 3 (MMP-3) 基因的转录。 NF-κB 已知是炎症反应的关键调节因子，但对 ZBP-89 的调节知之甚少。为了确定 ZBP-89 在炎症过程中是否受到调节，我们设计了实验来确定 ZBP-89 水平是否以及在何种程度上受到炎症细胞因子的影响。在这里，我们发现人成纤维细胞中的 ZBP-89 mRNA 和蛋白质表达受到炎症细胞因子白介素-1β 的显着抑制。由于 ZBP-89 水平的任何变化都可能影响 MMP-3 和其他 ZBP-89 靶基因的调节，因此这些结果为微调免疫反应所涉及的机制提供了重要的见解。
Zinc-binding protein-89 (ZBP-89; ZNF148, BERF-1, BFCOL-1) is a zinc-finger transcription factor of the Kruppel family. It has been shown to regulate the expression of a number of genes, acting as either an activator or repressor of gene expression, depending on the context. It is over-expressed in several cancers, but has been shown to be involved in apoptosis and to have a negative influence on cell growth in part by interactions with p53. Previously, ZBP-89 was shown to activate transcription of the matrix metalloproteinase-3 (MMP-3) gene by binding to a polymorphic promoter element in competition with nuclear factor κB (NF-κB). NF-κB is known to be a key regulator of the inflammatory response, but relatively little is known about regulation of ZBP-89. In order to ascertain whether ZBP-89 is regulated during inflammation, we designed experiments to determine whether and to what extent ZBP-89 levels are affected by inflammatory cytokines. Here we show that ZBP-89 mRNA and protein expression are significantly inhibited in human fibroblasts by the inflammatory cytokine interleukin-1β. Since any change in the levels of ZBP-89 would presumably impact the regulation of MMP-3 and other ZBP-89 target genes, these results provide important insight into mechanisms involved in fine-tuning the immune response.