Roles for interleukin-1beta, phorbol ester and a post-transcriptional regulator in the control of bradykinin B1 receptor gene expression.
Roles for interleukin-1beta, phorbol ester and a post-transcriptional regulator in the control of bradykinin B1 receptor gene expression.
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IL-1β、佛波醇酯和转录后调节因子在控制缓激肽 B1 受体基因表达中的作用。
DOI：
10.1042/bj3300361
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发表时间：
1998
期刊：
影响因子：
--
通讯作者：
Taylor,L
中科院分区：
文献类型：
--
作者：
Zhou,X;Polgar,P;Taylor,L
缓激肽B1受体（BKB 1 R）参与多种病理生理过程，特别是与炎症相关的过程。已知该受体的基因被白细胞介素（IL）-1β（一种促炎细胞因子）上调。然而，参与调控BKB 1 R基因表达的分子机制尚未确定。我们证明IL-1β诱导人胚肺成纤维细胞（IMR 90）中BKB 1 R mRNA水平和desArg 10-kallidin结合的快速增加。这种BKB 1 R mRNA水平的增加是蛋白质合成无关的，如用放线菌酮（CHX）或嘌呤霉素（PUR）处理细胞所示。通过检测IL-1β对BKB 1 R mRNA降解的影响，我们发现IL-1β上调BKB 1 R表达是通过转录激活和转录后mRNA稳定化实现的。除了IL-1β效应外，翻译抑制剂CHX和PUR通过抑制BKB 1 R mRNA降解增加稳态BKB 1 R mRNA水平。去除CHX块，随后恢复蛋白质合成，导致desArg 10-胰激肽结合的相当大的增加。使用信号通路抑制剂，我们发现IL-1β通过蛋白酪氨酸激酶发挥作用，而不是蛋白激酶C或蛋白激酶A。然而，激活蛋白激酶C的佛波醇12-肉豆蔻酸酯13-乙酸酯增加BKB 1 R mRNA的水平和desArg 10-胰激肽的结合。这种增加被NF-κB活化抑制剂阻断。
Bradykinin B1 receptor (BKB1R) is involved in a variety of pathophysiological processes, particularly those related to inflammation. The gene for this receptor is known to be upregulated by interleukin (IL)-1β, a proinflammatory cytokine. However, the molecular mechanisms involved in the regulation of the BKB1R gene expression have not been defined. We demonstrated that IL-1β induces a rapid increase in BKB1R mRNA level and the binding of desArg10-kallidin in human embryo lung fibroblasts (IMR90). This increase in BKB1R mRNA level is protein synthesis-independent as indicated by treatment of cells with cycloheximide (CHX) or puromycin (PUR). By testing the IL-1β effect on BKB1R mRNA degradation, we showed that the IL-1β upregulation of BKB1R expression is achieved through both transcriptional activation and post-transcriptional mRNA stabilization. In addition to the IL-1β effects, translation inhibitors, CHX and PUR increase the steady state BKB1R mRNA level by inhibiting BKB1R mRNA degradation. Removal of the CHX block with subsequent resumption of protein synthesis results in a sizable increase of desArg10-kallidin binding. Using signalling pathway inhibitors, we show that IL-1β functions through a protein tyrosine kinase, not protein kinase C or protein kinase A. However, activation of protein kinase C by phorbol 12-myristate 13-acetate increases the level of BKB1R mRNA and the binding of desArg10-kallidin. This increase is blocked by NF-κB activation inhibitors.