Transcriptional role of the nuclear factor κB site in the induction by lipopolysaccharide and suppression by dexamethasone of cyclooxygenase-2 in U937 cells
Transcriptional role of the nuclear factor κB site in the induction by lipopolysaccharide and suppression by dexamethasone of cyclooxygenase-2 in U937 cells
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DOI：
10.1006/bbrc.1998.8222
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发表时间：
1998-03-06
影响因子：
3.1
通讯作者：
Tanabe, T
中科院分区：
文献类型：
--
作者：
Inoue, H;Tanabe, T
环氧化酶-2 （COX-2）是环氧化酶的诱导同型酶，在单核细胞分化的U937细胞中受脂多糖（LPS）的选择性表达，其表达受到糖皮质激素地塞米松（DEX）的抑制，但在细胞分化前LPS未检测到COX-2 mRNA，也未诱导COX-2 mRNA表达。为了研究COX-2基因中NF-kappa B位点（核苷酸-223 ~ -214）的转录作用，将cAMP应答元件和NF-IL6位点同时发生突变的COX-2启动子区域（核苷酸-327 ~ +59）驱动的荧光素酶报告载体稳定转染到U937细胞中。在未分化的细胞中观察到大量的荧光素酶活性未被LPS诱导，但在细胞分化后，LPS诱导荧光素酶活性，DEX抑制其诱导作用。此外，蛋白酪氨酸激酶抑制剂herbimycin a同时抑制LPS诱导的COX-2 mRNA表达和荧光素酶活性。这些结果表明NF-kappa B位点以分化依赖的方式参与LPS诱导的COX-2基因表达和DEX和herbimycin a对COX-2基因的抑制。(C) 1998学术出版社。
Cyclooxygenase-2 (COX-2), an inducible isozyme of cyclooxygenase, is selectively expressed in response to lipopolysaccharide (LPS) and its expression is suppressed by the glucocorticoid dexamethasone (DEX) in the monocytic differentiated U937 cells, However, COX-2 mRNA was not detected nor induced by LPS before the cells differentiated. To study the transcriptional role of the NF-kappa B site (nucleotides -223 to -214) in the COX-2 gene, the luciferase reporter vector driven by the COX-2 promoter region (nucleotides -327 to +59) mutated at both the cAMP response element and the NF-IL6 site was stably transfected into U937 cells. The substantial luciferase activity observed in the undifferentiated cells was not induced by LPS, However, after the cells had differentiated, luciferase activity was induced by LPS and its induction was suppressed by DEX. Moreover, a protein tyrosine kinase inhibitor herbimycin A suppressed both the expression of COX-2 mRNA and the luciferase activity induced by LPS, These results suggest that the NF-kappa B site is involved in both the LPS-induced expression of the COX-2 gene and its suppression by DEX and herbimycin A in a differentiation-dependent manner. (C) 1998 Academic Press.