An in vivo cytokine and endotoxin-independent pathway for induction of nitric oxide synthase II mRNA, enzyme, and nitrate/nitrite in alveolar macrophages.
An in vivo cytokine and endotoxin-independent pathway for induction of nitric oxide synthase II mRNA, enzyme, and nitrate/nitrite in alveolar macrophages.
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用于诱导肺泡巨噬细胞中一氧化氮合酶 II mRNA、酶和硝酸盐/亚硝酸盐的体内细胞因子和内毒素独立途径。
DOI：
10.1006/bbrc.1996.1483
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发表时间：
1996
影响因子：
3.1
通讯作者：
Giles,TD
中科院分区：
文献类型：
--
作者：
Greenberg,SS;Xie,J;Zhao,X;Jie,O;Giles,TD
在支气管肺泡灌洗 (BAL) 前两小时，通过气管内 (i.t.) 给予大鼠二丁酰环 AMP（DB-cAMP，0.1 和 1.0 mg/kg）和嘌呤 2-受体激动剂甲硫基-ATP（MT-ATP mg/kg），使 iNOS mRNA 增加至等于或大于 iNOS mRNA 产生的水平。 LPS，不会引起中性粒细胞浸润到肺泡腔或上调肿瘤坏死因子 α (TNFα)。 DB-cAMP 和 MT-ATP 刺激的 iNOS mRNA 翻译成蛋白质以及激活 iNOS 产生 RNI 的速度比 LPS 刺激的 iNOS mRNA 慢。二乙基二硫代氨基甲酸酯（5 mg/kg，i.t.）是一种活性氧中间体螯合剂和 NFkappaB 抑制剂，可减弱 LPS 诱导的 iNOS mRNA 上调，而不影响 DB-cAMP 或 MT-ATP 产生的 iNOS mRNA 上调。我们得出的结论是，体内存在一条不依赖LPS和细胞因子的iNOS mRNA转录途径，该途径可以直接被DB-cAMP和嘌呤-2受体刺激激活。在哮喘患者和患有其他疾病且接受影响 cAMP 和嘌呤系统的药物治疗的患者中发现的 iNOS 增加可能是医源性的，而不是致病性的。
Dibutyryl cyclic AMP (DB-cAMP, 0.1 and 1.0 mg/kg) and the purine-2-receptor agonist methyl-thio-ATP (MT-ATP mg/kg) given by intratracheal (i.t.) administration to rats two hr before bronchoalveolar lavage (BAL) increased iNOS mRNA to be equal to or greater than that produced by i.t. LPS, without eliciting neutrophil infiltration into the alveolar space or the upregulation of tumor necrosis factor alpha (TNFα). Translation of DB-cAMP and MT-ATP-stimulated iNOS mRNA into protein and activation of iNOS to produce RNI was slower than that resulting from LPS-stimulated iNOS mRNA. Diethyldithiocarbamate (5 mg/kg, i.t.) a sequestrant of reactive oxygen intermediates and an inhibitor of NFkappaB attenuated LPS-induced upregulation of iNOS mRNA without affecting that produced by DB-cAMP or MT-ATP. We conclude that an LPS and cytokine-independent pathway of transcription of iNOS mRNA existsin vivo,which can be directly activated by DB-cAMP and purine-2 receptor stimulation. It is possible that the increase in iNOS found in asthmatic patients and those with other diseases that are treated with drugs which affect the cAMP and purine systems may be iatrogenic rather than pathogenetic in origin.