Inducible nitric oxide synthase is not required in the development of endotoxin tolerance in mice.
Inducible nitric oxide synthase is not required in the development of endotoxin tolerance in mice.
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小鼠内毒素耐受性的发展不需要诱导型一氧化氮合酶。
DOI：
10.1097/00024382-200206000-00007
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发表时间：
2002
期刊：
影响因子：
--
通讯作者：
Cook,JamesA
中科院分区：
文献类型：
--
作者：
Zingarelli,Basilia;Hake,PaulW;Cook,JamesA
我们研究了诱导型一氧化氮合酶(INOS)在内毒素耐受中的作用，这种耐受是由诱导型一氧化氮合酶(iNOS−/−)基因缺陷的小鼠和野生型窝产仔诱导的。在不耐受的野生型小鼠中，内毒素导致高死亡率，血浆亚硝酸盐和硝酸盐水平升高，肿瘤坏死因子α和白介素10(IL-10)水平升高。在这些事件之前，抑制物核因子B受体(κBα，IκBα)和核因子B受体(κBβ，IκBβ)的降解以及核因子-κB(NF-κB)在肺中的激活。在给予致死性内毒素之前，用亚致死剂量的内毒素对野生型小鼠进行预处理，可改善致死性并钝化肿瘤坏死因子α的产生，而IL-10、亚硝酸盐和硝酸盐的产生保持不变。这些事件与I-κBα降解减少和肺组织中核因子-κB活化有关。I-κ-B-β的降解动力学也发生改变。在平行实验中，不耐受的诱导型一氧化氮合酶−/−小鼠在内毒素作用下的死亡率与不耐受的野生型小鼠相似。致死性内毒素注射后，血浆亚硝酸盐和硝酸盐水平未见升高。与不耐受的野生型小鼠相比，IL-10水平显著降低，而肿瘤坏死因子α水平同样升高。在这些事件发生之前，IκBα的降解较轻，肺组织中的NF-κB活性降低。诱导型一氧化氮合酶−/−小鼠用亚致死性内毒素预处理可改善其致死率。与不耐受的诱导型一氧化氮合酶α小鼠相比，肿瘤坏死因子−/−的产生显著减少，而IL-10的产生显著增加。内毒素耐受不改变肺组织IκBα的降解和核因子κB的激活，而IκBβ的降解动力学仅延迟。我们的数据表明，诱导型一氧化氮合酶不是内毒素耐受形成所必需的，在缺乏诱导型一氧化氮合酶的情况下，其他信号转导途径而不是核因子-κB可能调节内毒素耐受性的诱导。
We investigated the role of inducible nitric oxide synthase (iNOS) in endotoxin tolerance, which was induced in mice genetically deficient of iNOS (iNOS−/−) and in wild-type littermates. In non-tolerant wild-type mice, endotoxin induced high mortality, elevation of plasma levels of nitrite and nitrate, tumor necrosis factor α (TNFα), and interleukin 10 (IL-10). These events were preceded by degradation of inhibitors κBα (IκBα) and κBβ (IκBβ), and activation of nuclear factor-κB (NF-κB) in the lung. Pretreatment of wild-type mice with a sublethal dose of endotoxin prior to lethal endotoxin administration ameliorated lethality and blunted TNFα production, whereas IL-10, nitrite, and nitrate production was maintained. These events were associated with reduction of IκBα degradation and NF-κB activation in the lung. The kinetics of degradation of IκBβ were also altered. In parallel experiments, nontolerant iNOS−/− mice experienced similar mortality after endotoxin as nontolerant wild-type mice. Plasma levels of nitrite and nitrate were not elevated after lethal endotoxin administration. IL-10 levels were significantly reduced in comparison to nontolerant wild-type mice, whereas TNFα levels were similarly increased. These events were preceded by lesser degradation of IκBα and reduced NF-κB activation in the lung. Pretreatment of iNOS−/− mice with a sublethal endotoxin ameliorated lethality. TNFα production was significantly reduced, whereas IL-10 production was significantly increased when compared to nontolerant iNOS−/− mice. Degradation of IκBα and activation of NF-κB in the lung were not altered by endotoxin tolerance, whereas kinetics of IκBβ degradation was only delayed. Our data suggests that iNOS is not required for the development of endotoxin tolerance, and that other signal transduction pathways, rather than NF-κB, may regulate induction of endotoxin tolerance in the absence of iNOS.
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DOI：
10.1056/nejm198110083051503
发表时间：
1981
期刊：
The New England journal of medicine
影响因子：
--
作者：
Sylvester,RJ;Pinedo,HM;DePauw,M;Staquet,MJ;Buyse,ME;Renard,J;Bonadonna,G
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Bonadonna,G
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影响因子：
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作者：
A. Oliveras;Juanjo Hernández;Carme Camps;L. Fontdevila;Victoria Vega;E. Vinyoles;I. Galcerán;Marta Crespo;S. Vázquez
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DOI：
10.1288/00005537-198511000-00017
发表时间：
1985
期刊：
The Laryngoscope
影响因子：
--
作者：
J. Jacobs;E. Spitznagel;D. Sessions
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DOI：
10.1016/0010-4809(81)90042-2
发表时间：
1981
期刊：
Computers and biomedical research, an international journal
影响因子：
--
作者：
D. Wirtschafter;M. Scalise;C. Henke;R. Gams
通讯作者：
R. Gams