Enhancement of prostaglandin D2 production through cyclooxygenase-2 and lipocalin-type prostaglandin D synthase by upstream stimulatory factor 1 in human brain-derived TE671 cells under serum starvation
Enhancement of prostaglandin D2 production through cyclooxygenase-2 and lipocalin-type prostaglandin D synthase by upstream stimulatory factor 1 in human brain-derived TE671 cells under serum starvation
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DOI：
10.1016/j.gene.2008.08.023
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发表时间：
2008-12-15
期刊：
影响因子：
3.5
通讯作者：
Urade, Yoshihiro
中科院分区：
文献类型：
--
作者：
Fujimori, Ko;Aritake, Kosuke;Urade, Yoshihiro
我们发现，在缺乏血清的条件下，环氧合酶(COX)-2和Lipocalin型PGD合成酶(L-PGDS)基因的转录激活可以诱导人脑源性TE671细胞产生前列腺素(PG)D-2。对人L-PGDS基因启动子和内含子区域的分析表明，内含子4中的非典型E-box介导了血清饥饿诱导L-PGDS基因表达上调。凝胶迁移率改变实验和染色质免疫沉淀实验结果表明，上游刺激因子(USF)1与该非典型E盒结合。在血清饥饿条件下，TE671细胞中USF1基因的表达也通过激活p38丝裂原活化蛋白激酶而增强，并且血清饥饿使USF1与非典型E-box结合的效率明显提高。USF1siRNA抑制L-PGDS和COX-2基因的表达及PGD(2)的产生。此外，COX-2抑制剂NS-398和L-PGDS抑制剂AT-56可抑制血清饥饿条件下培养的TE671细胞PGD(2)的产生。这些结果表明，血清饥饿刺激TE671细胞产生PGD(2)是由COX-2和L-PGDS通过增强USF1介导的。(C)2008爱思唯尔B.V.保留所有权利。
We found that prostaglandin (PG) D-2 production was induced through transcriptional activation of cyclooxygenase (COX)-2 and lipocalin-type PGD synthase (L-PGDS) genes under serum-starved conditions in human brain-derived TE671 cells. Analysis of promoter and intron regions of the human L-PGDS gene demonstrated that an atypical E-box within intron 4 mediated serum starvation-induced up-regulation of L-PGDS gene expression. The results of electrophoretic mobility shift assay and chromatin immunoprecipitation assay showed that upstream stimulatory factor (USF) 1 bound to this atypical E-box. USF1 gene expression was also enhanced during serum starvation in TE671 cells through activation of p38 mitogen activated protein kinase, and the efficiency of the binding of USF1 to the atypical E-box was clearly increased by serum starvation. Administration of USF1 siRNA suppressed both L-PGDS and COX-2 gene expression and PGD(2) production. Moreover, NS-398, a COX-2 inhibitor and AT-56, an L-PGDS inhibitor, suppressed PGD(2) production in TE671 cells cultured under the serum-starved condition. These results indicate that PGD(2) production stimulated by serum starvation is mediated by both COX-2 and L-PGDS through enhancement of USF1 in TE671 cells. (c) 2008 Elsevier B.V. All rights reserved.