MACROPHAGE NITRIC-OXIDE SYNTHASE IS A GLUCOCORTICOID-INHIBITABLE PRIMARY RESPONSE GENE IN 3T3 CELLS
MACROPHAGE NITRIC-OXIDE SYNTHASE IS A GLUCOCORTICOID-INHIBITABLE PRIMARY RESPONSE GENE IN 3T3 CELLS
复制标题
DOI：
10.1002/jcp.1041570117
复制
发表时间：
1993-10-01
影响因子：
5.6
通讯作者：
HERSCHMAN, HR
中科院分区：
文献类型：
--
作者：
GILBERT, RS;HERSCHMAN, HR
一氧化氮和胰头素都是细胞间通讯的强旁分泌介质。一氧化氮合酶（mac-NOS）的内毒素-脂多糖（LPS）诱导型最近已从小鼠巨噬细胞克隆。从3 T3细胞克隆的诱导型前列腺素合酶（TIS 10/PGS-2）也在LPS激活的巨噬细胞中诱导。由于广泛的配体，诱导3 T3细胞中的主要反应基因，嵌合启动子结构的研究在3 T3细胞中的容易性，以及一氧化氮和三尖杉脂素作为旁分泌介质的重要性，我们研究了mac-NOS在3 T3细胞中的表达。十四酰佛波醇-13-乙酸酯（TPA），毛喉素，血小板衍生生长因子，成纤维细胞生长因子，和血清都诱导mac-NOS在瑞士3 T3细胞的表达。因此，mac-NOS基因可以响应范围更广的诱导剂比以前怀疑。mac-NOS是一个主要的反应基因;放线菌酮不阻断诱导。TPA诱导的mac-NOS和TIS 10/PGS-2 mRNA积累模式相似。LPS是Swiss 3 T3细胞中mac-NOS的有效诱导剂，但不能诱导TIS 10/PGS-2。相反，在含有温度敏感性v-src基因的BALB/c 3 T3细胞系中，v-src表达诱导TIS 10/PGS-2信息，但不诱导iNOS信息。地塞米松（DEX）阻止TIS 10/PGS-2的诱导，但不能阻止大多数其他初级应答基因的诱导。DEX还阻断Swiss 3 T3细胞中的mac-NOS诱导。可诱导的TIS 10/PGS-2和mac-NOS基因，负责两种不同的旁分泌剂的生产，似乎在3 T3细胞中共享许多监管功能。(C)1993 Wiley-Liss，Inc.
Both nitric oxide and prostaglandins are potent paracrine mediators of intercellular communication. An endotoxin-lipopolysaccharide (LPS) inducible form of nitric oxide synthase (mac-NOS) has recently been cloned from murine macrophages. An inducible prostaglandin synthase (TIS10/PGS-2), cloned from 3T3 cells, is also induced in LPS-activated macrophage. Because of the wide range of ligands that induce primary response genes in 3T3 cells, the ease of studying chimeric promoter constructs in 3T3 cells, and the importance of both nitric oxide and prostaglandins as paracrine mediators, we examined expression of mac-NOS in 3T3 cells. Tetradecanoyl phorbol-13-acetate (TPA), forskolin, platelet-derived growth factor, fibroblast growth factor, and serum all induce mac-NOS expression in Swiss 3T3 cells. Thus the mac-NOS gene can respond to a far wider range of inducers than previously suspected. mac-NOS is a primary response gene; cycloheximide does not block induction. TPA-induced mac-NOS and TIS10/PGS-2 mRNA accumulation patterns are similar. LPS is a potent inducer of mac-NOS in Swiss 3T3 cells but cannot induce TIS10/PGS-2. In contrast, v-src expression induces TIS10/PGS-2 message, but not iNOS message in a BALB/c 3T3 cell line containing a temperature-sensitive v-src gene. Dexamethasone (DEX) prevents induction of TIS10/PGS-2, but not most other primary response genes. DEX also blocks mac-NOS induction in Swiss 3T3 cells. The inducible TIS10/PGS-2 and mac-NOS genes, responsible for the production of two distinct paracrine agents, appear to share many regulatory features in 3T3 cells. (C) 1993 Wiley-Liss, Inc.