Cigarette smoke-induced expression of heme oxygenase-1 in human lung fibroblasts is regulated by intracellular glutathione
Cigarette smoke-induced expression of heme oxygenase-1 in human lung fibroblasts is regulated by intracellular glutathione
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DOI：
10.1152/ajplung.90215.2008
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发表时间：
2008-10-01
影响因子：
4.9
通讯作者：
Phipps, Richard P.
中科院分区：
文献类型：
--
作者：
Baglole, Carolyn J.;Sime, Patricia J.;Phipps, Richard P.
Baglole CJ，Sime PJ，Phipps RP.香烟烟雾诱导的人肺成纤维细胞血红素氧合酶-1表达受细胞内谷胱甘肽调节。美国生理学杂志肺细胞分子生理学295：L624-L636，2008年。首次发表于2008年8月8日; doi：10.1152/ajplung.90215.2008。成纤维细胞是关键的结构细胞，可以被香烟烟雾破坏。香烟烟雾中含有许多能够引起氧化应激的成分，这些成分可以诱导血红素加氧酶（HO）-1，一种细胞保护酶。没有关于香烟烟雾提取物（CSE）暴露后原代人肺成纤维细胞中HO-1表达的数据。我们假设暴露于香烟烟雾的人肺成纤维细胞会通过细胞内谷胱甘肽（GSH）的变化来增加HO-1。将原代人肺成纤维细胞暴露于CSE，并评估HO-1表达和GSH水平的变化。在两种不同的原代人肺成纤维细胞株中，CSE诱导HO-1表达的时间和剂量依赖性增加，但不诱导HO-2或胆绿素还原酶的表达，这是一项新发现。HO-1的这种诱导导致细胞内GSH的减少，并且GSH的持续减少导致HO-1的急剧增加。用抗氧化剂N-乙酰-L-半胱氨酸或GSH处理减少CSE诱导的HO-1表达。我们还研究了负责HO-1诱导的信号转导机制。核因子红细胞衍生2，如2（Nrf2）不参与CSE诱导HO-1。激活蛋白-1（AP-1）是一种氧化还原敏感的转录因子，在其他系统中显示可调节HO-1的表达。CSE暴露导致AP-1的两个关键成分c-Fos和c-Jun在核内积累。SP-600125减少c-Fos和c-Jun核转位减弱了CSE诱导的HO-1表达。这些数据支持了香烟烟雾引起的细胞氧化还原状态变化诱导成纤维细胞中HO-1的概念。HO-1的这种增加可能有助于防止香烟烟雾诱导的炎症和/或细胞死亡。
Baglole CJ, Sime PJ, Phipps RP. Cigarette smoke-induced expression of heme oxygenase-1 in human lung fibroblasts is regulated by intracellular glutathione. Am J Physiol Lung Cell Mol Physiol 295: L624-L636, 2008. First published August 8, 2008; doi: 10.1152/ajplung.90215.2008.-Fibroblasts are key structural cells that can be damaged by cigarette smoke. Cigarette smoke contains many components capable of eliciting oxidative stress, which may induce heme oxygenase (HO)-1, a cytoprotective enzyme. There are no data on HO-1 expression in primary human lung fibroblasts after cigarette smoke extract (CSE) exposure. We hypothesized that human lung fibroblasts exposed to cigarette smoke would increase HO-1 though changes in intracellular glutathione (GSH). Primary human lung fibroblasts were exposed to CSE, and changes in HO-1 expression and GSH levels were assessed. CSE induced a time- and dose-dependent increase in expression of HO-1, but not HO-2 or biliverdin reductase, in two different primary human lung fibroblast strains, a novel finding. This induction of HO-1 paralleled a decrease in intracellular GSH, and a sustained reduction in GSH resulted in a dramatic increase in HO-1. Treatment with the antioxidants N-acetyl-L- cysteine or GSH reduced the expression of HO-1 induced by CSE. We also examined the signal transduction mechanism responsible for HO-1 induction. Nuclear factor erythroid-derived 2, like 2 (Nrf2) was not involved in HO-1 induction by CSE. Activator protein-1 (AP-1) is a redox-sensitive transcription factor shown in other systems to regulate HO-1 expression. CSE exposure resulted in nuclear accumulation of c-Fos and c-Jun, two key AP-1 components. Reduction of c-Fos and c-Jun nuclear translocation by SP-600125 attenuated the CSE-induced expression of HO-1. These data support the concept that changes in the cellular redox status brought on by cigarette smoke induce HO-1 in fibroblasts. This increase in HO-1 may help protect against cigarette smoke-induced inflammation and/or cell death.