INDUCTION OF CERULOPLASMIN GENE-EXPRESSION IN RAT LUNG DURING INFLAMMATION AND HYPEROXIA
INDUCTION OF CERULOPLASMIN GENE-EXPRESSION IN RAT LUNG DURING INFLAMMATION AND HYPEROXIA
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DOI：
10.1152/ajplung.1991.260.2.l68
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发表时间：
1991-02-01
影响因子：
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通讯作者：
GITLIN, JD
中科院分区：
文献类型：
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作者：
FLEMING, RE;WHITMAN, IP;GITLIN, JD
为了确定炎症对肝外铜蓝蛋白基因表达的影响，我们检测了内毒素注射后成年大鼠组织中铜蓝蛋白mRNA的含量。在给药后8小时内，肝脏内的内毒素铜蓝蛋白mRNA含量如预期的那样增加，在肺部也可以检测到。内毒素的作用是组织特异性的，因为铜蓝蛋白mRNA在其他肝外组织中并不一致。铜蓝蛋白mRNA在肺和肝组织中的积累动力学相似，24 h内各组织中铜蓝蛋白mRNA含量最多增加7 - 9倍。在内毒素作用3 h内，两组织中铜蓝蛋白基因转录的相对速率均增加，表明炎症期间铜蓝蛋白基因表达的调节机制相似。肺泡巨噬细胞是炎症肺中铜蓝蛋白产生的一个细胞位点，在体外对内毒素的反应中，巨噬细胞表达铜蓝蛋白基因并合成铜蓝蛋白。由于这些发现，我们也研究了高氧对铜蓝蛋白基因表达的影响。成年大鼠暴露于95% O2环境下，肺组织中铜蓝蛋白mRNA在46小时内被诱导5 - 6倍，这种反应是时间依赖性的，在86小时达到最大值。铜蓝蛋白mRNA的高氧诱导是肺特异性的，而不是全系统炎症的结果，因为肝脏铜蓝蛋白mRNA含量保持不变。这些数据表明，肺是炎症和高氧时铜蓝蛋白基因表达的重要部位，并提示该蛋白可能在肺损伤或修复中起着以前未被认识到的作用。
To determine the effect of inflammation on extrahepatic ceruloplasmin gene expression we examined the ceruloplasmin mRNA content of adult rat tissues after endotoxin injection. Within 8 h of a dose of endotoxin ceruloplasmin mRNA content increased in the liver as expected and was also detectable in the lung. The effect of endotoxin was tissue specific because ceruloplasmin mRNA was not consistently detected in other extrahepatic tissues. The kinetics of ceruloplasmin mRNA accumulation in lung and liver tissue were similar with a maximum seven- to ninefold increase in ceruloplasmin mRNA content in each tissue within 24 h. The relative rate of ceruloplasmin gene transcription was increased in both tissues within 3 h of endotoxin, suggesting similar mechanisms of regulation of ceruloplasmin gene expression during inflammation. One cellular site of ceruloplasmin production in the inflamed lung was found to be the alveolar macrophage, which expressed the ceruloplasmin gene and synthesized ceruloplasmin protein in response to endotoxin in vitro. Because of these findings we also examined the effects of hyperoxia on ceruloplasmin gene expression. Exposure of adult rats to 95% O2 resulted in a five- to sixfold induction of ceruloplasmin mRNA in lung tissue within 46 h, and this response was time dependent, reaching maximum values at 86 h. Hyperoxic induction of ceruloplasmin mRNA was specific to the lung and not the result of systemic inflammation because hepatic ceruloplasmin mRNA content remained constant. These data indicate that the lung is a prominent site of ceruloplasmin gene expression during inflammation and hyperoxia and suggest that this protein may play a previously unappreciated role in pulmonary injury or repair.