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首页> 外文期刊>American Journal of Physiology >The aryl hydrocarbon receptor is a regulator of cigarette smoke induction of the cyclooxygenase and prostaglandin pathways in human lung fibroblasts.
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The aryl hydrocarbon receptor is a regulator of cigarette smoke induction of the cyclooxygenase and prostaglandin pathways in human lung fibroblasts.

机译：芳基烃受体是香烟烟雾诱导人肺成纤维细胞中环氧合酶和前列腺素途径的调节剂。

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摘要

Cigarette smoking can lead to chronic lung inflammation and lung cancer. Chronic inflammation, associated with expression of cyclooxygenase-2 (COX-2) and prostaglandins, predisposes to malignancy. We recently demonstrated that human lung fibroblasts are activated by cigarette smoke to express COX-2 and prostaglandin E(2) (PGE(2)). Little is known about the mechanism whereby smoke activates human lung fibroblasts to produce proinflammatory mediators. Herein, we report the central role of the aryl hydrocarbon receptor (AHR) in cigarette smoke extract (CSE)-induced COX-2, microsomal PGE(2) synthase (mPGES), and PGE(2) production in human lung fibroblasts. Western blot analysis revealed that primary strains of human lung fibroblasts express AHR and aryl hydrocarbon nuclear translocator protein, supporting the possibility that smoke activates lung fibroblasts through this pathway. Experiments were subsequently performed to determine whether the AHR was activated by CSE. Immunocytochemistry and EMSA analysisrevealed that CSE induced nuclear translocation of the AHR in human lung fibroblasts. CSE decreased protein levels of the AHR, consistent with AHR ligand-induced proteosome-mediated degradation. CSE also induced mPGES-1 and COX-2 protein and increased PGE(2) production. Treatment of human fibroblasts with AHR antagonists in the presence of CSE inhibited AHR nuclear translocation as well as COX-2, mPGES-1, and PGE(2) production. These data indicate that the AHR pathway plays an important role in cigarette smoke-mediated COX-2 and PG production in human lung fibroblasts and may contribute to tobacco-associated inflammation and lung disease.
机译：吸烟会导致慢性肺部炎症和肺癌。慢性炎症与环氧合酶2（COX-2）和前列腺素的表达有关，易患恶性肿瘤。我们最近证明，人类的肺成纤维细胞被香烟烟雾激活以表达COX-2和前列腺素E（2）（PGE（2））。关于烟雾激活人肺成纤维细胞产生促炎性介质的机制知之甚少。在这里，我们报告了芳烃受体（AHR）在香烟烟雾提取物（CSE）诱导的COX-2，微粒体PGE（2）合酶（mPGES）和PGE（2）生产在人类肺成纤维细胞中的核心作用。 Western印迹分析显示，人肺成纤维细胞的主要菌株表达AHR和芳基碳氢核转运蛋白，支持烟雾通过该途径激活肺成纤维细胞的可能性。随后进行实验以确定AHR是否被CSE激活。免疫细胞化学和EMSA分析表明，CSE诱导了人肺成纤维细胞中AHR的核易位。 CSE降低了AHR的蛋白质水平，这与AHR配体诱导的蛋白体介导的降解相一致。 CSE还诱导了mPGES-1和COX-2蛋白并增加了PGE（2）的产生。在CSE存在下用AHR拮抗剂治疗人成纤维细胞会抑制AHR核移位以及COX-2，mPGES-1和PGE（2）的产生。这些数据表明，AHR途径在人肺成纤维细胞中的香烟烟雾介导的COX-2和PG产生中起重要作用，并且可能与烟草相关的炎症和肺部疾病有关。

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