Plasma from hemorrhaged mice activates CREB and increases cytokine expression in lung mononuclear cells through a xanthine oxidase-dependent mechanism.
Plasma from hemorrhaged mice activates CREB and increases cytokine expression in lung mononuclear cells through a xanthine oxidase-dependent mechanism.
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失血小鼠的血浆通过黄嘌呤氧化酶依赖性机制激活 CREB 并增加肺单核细胞中的细胞因子表达。
DOI：
10.1165/ajrcmb.14.2.8630271
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发表时间：
1996
期刊：
影响因子：
--
通讯作者：
Abraham,E
中科院分区：
文献类型：
--
作者：
Shenkar,R;Abraham,E
失血迅速增加血浆黄嘌呤氧化酶水平以及肺内促炎症和免疫调节细胞因子的表达。为了确定循环黄嘌呤氧化酶(XO)以及其他血浆因素在影响肺细胞因子表达中的作用，我们进行了一项研究，将出血性小鼠的血浆转移到非出血性受者体内。给受体小鼠注射出血后血浆可增加肺单个核细胞中白细胞介素1β(IL-1β)、肿瘤坏死因子-α(TNF-α)和转化生长因子-β1(TGF-β1)的mRNA水平。在接受别嘌醇处理的出血后血浆或在转移出血后血浆之前喂食富钨、低氧饮食的小鼠的肺中，没有发现这些细胞因子的mRNA水平增加。在所检测的核转录调节因子中，只有cAMP反应元件结合蛋白(CREB)在给予出血后血浆的小鼠肺单个核细胞的核提取物中被激活。未见核因子-kappaB、核因子-白介素6、活化蛋白-1、血清蛋白-1的激活。这些结果表明，失血诱导肺细胞因子表达增加的机制是通过血浆介质启动的组织XO依赖的途径激活增强子CREB。
Hemorrhage rapidly increases plasma xanthine oxidase levels as well as the expression of proinflammatory and immunoregulatory cytokines in the lungs. To determine the role of circulating xanthine oxidase (XO), as well as other plasma factors, in affecting pulmonary cytokine expression, we conducted studies in which plasma from hemorrhaged mice was transferred into unhemorrhaged recipient mice. Administration of posthemorrhage plasma to recipient mice increased the levels of mRNA for interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), and transforming growth factor-beta 1 (TGF-beta 1) in lung mononuclear cells. No enhancement of mRNA levels for these cytokines was found in the lungs of mice given allopurinol-treated posthemorrhage plasma or fed a tungsten-enriched, XO-depleting diet prior to transfer of posthemorrhage plasma. Among the nuclear transcriptional regulatory factors examined, only the cyclic AMP response-element binding protein (CREB) was activated in nuclear extracts from lung mononuclear cells of mice that were given posthemorrhage plasma. No activation of nuclear factor-kappa B (NF-kappa B), nuclear factor interleukin 6 (NF-IL6), activating protein-1 (AP-1), or serum protein-1 (SP-1) was found. These results suggest that the mechanism for hemorrhage-induced increases in pulmonary cytokine expression is by activation of the enhancer CREB through a tissue XO-dependent pathway initiated by plasma-borne mediators.