Hemorrhage increases cytokine expression in lung mononuclear cells in mice - Involvement of catecholamines in nuclear factor-kappa B regulation and cytokine expression
Hemorrhage increases cytokine expression in lung mononuclear cells in mice - Involvement of catecholamines in nuclear factor-kappa B regulation and cytokine expression
复制标题
DOI：
10.1172/jci119314
复制
发表时间：
1997-04-01
影响因子：
15.9
通讯作者：
Abraham, E
中科院分区：
文献类型：
--
作者：
LeTulzo, Y;Shenkar, R;Abraham, E
出血后肺中促炎细胞因子和免疫调节细胞因子的表达迅速增加，这种变化导致急性炎性肺损伤的频繁发生。失血还导致肺循环和体循环中的儿茶酚胺浓度升高。在本实验中，我们使用α-和β-肾上腺素能受体阻断剂来检查血管紧张素诱导的肾上腺素能刺激和肺细胞因子表达之间的体内相互作用。用α-肾上腺素能受体拮抗剂酚妥拉明治疗小鼠不仅防止了IL-1 β，TNF-α，和TGF-β 1，IL-1 β蛋白的增加，以及核因子（NF）-κ B和环AMP反应元件结合蛋白的活化，这在出血后第一小时内发生在未治疗动物的肺细胞中。相反，在出血前用β-肾上腺素能受体拮抗剂普萘洛尔治疗与IL-1 β、TNF-α和TGF-β 1的mRNA水平的增加有关，其高于未治疗的肺老化小鼠中存在的水平，并且不能防止肺出血相关的肺IL-1 β蛋白的增加。用普萘洛尔治疗防止了肺出血诱导的环AMP反应元件结合蛋白的磷酸化，但增加了与创伤相关的NF-κ B活化。这些结果表明，出血最初通过α-肾上腺素能刺激而不是β-肾上腺素能刺激增加肺细胞因子表达，并表明这种α-肾上腺素能介导的效应通过激活转录调节因子NF-κ B发生。
The expression of proinflammatory and immunoregulatory cytokines rapidly increases in the lungs after hemorrhage, and such alterations contribute to the frequent development of acute inflammatory lung injury in this setting. Blood loss also produces elevations in catecholamine concentrations in the pulmonary and systemic circulation, In the present experiments, we used alpha- and beta-adrenergic receptor blockade to examine in vivo interactions between hemorrhage-induced adrenergic stimulation and pulmonary cytokine expression, Treatment of mice with the alpha-adrenergic receptor antagonist phentolamine prevented not only the elevation in mRNA levels of IL-1 beta, TNF-alpha, and TGF-beta 1, the increase in IL-1 beta protein, but also the activation of nuclear factor (NF)-kappa B and cyclic AMP response element binding protein, which occurred in lung cells of untreated animals during the first hour after hemorrhage. in contrast, treatment before hemorrhage with the beta-adrenergic receptor antagonist propranolol was associated with increases in mRNA levels for IL-1 beta, TNF-alpha, and TGF-beta 1, which were greater than those present in untreated hemorrhaged mice, and did mot prevent hemorrhage-associated increases in lung IL-1 beta protein, Treatment with propranolol prevented hemorrhage-induced phosphorylation of cyclic AMP response element binding protein, but increased hemorrhage-associated activation of NF-kappa B. These results demonstrate that hemorrhage initially increases pulmonary cytokine expression through alpha- but not beta-adrenergic stimulation, and suggest that such alpha-adrenergic-mediated effects occur through activation of the transcriptional regulatory factor NF-kappa B.