Expression and regulation of cyclooxygenase-2 in rat microglia
Expression and regulation of cyclooxygenase-2 in rat microglia
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DOI：
10.1111/j.1432-1033.1997.00726.x
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发表时间：
1997-02-01
期刊：
影响因子：
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通讯作者：
Fiebich, BL
中科院分区：
文献类型：
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作者：
Bauer, MKA;Lieb, K;Fiebich, BL
前列腺素水平的增加与各种神经病理学疾病有关，尽管对它们在大脑内的细胞来源知之甚少。在这项研究中，我们分析了环氧化酶-2（考克斯-2），花生四烯酸代谢的关键酶，在大鼠小胶质细胞的表达。考克斯-2 mRNA和蛋白以及前列腺素E（2）的形成在未刺激的小胶质细胞培养中几乎检测不到，但发现在对脂多糖的反应中强烈上调。然而，与大多数外周细胞相反，促炎细胞因子如肿瘤坏死因子α、白细胞介素-1 β或白细胞介素-6未能显著诱导考克斯-2表达。通过分析转录核因子-κ B（NF-κ B B）观察到类似的效果，NF-κ B在小胶质细胞中被脂多糖强烈激活，但与细胞因子孵育时没有。此外，已知的NF-κ B活化抑制剂，如地塞米松和抗氧化剂吡咯烷二硫代氨基甲酸酯，以及蛋白激酶C（PKC）抑制剂Go 6976，强烈地降低脂多糖诱导的COX-2转录，表明NF-κ B和PKC参与考克斯-2表达。我们的研究结果表明，小胶质细胞可能是脑中前列腺素类的重要来源，从而加强了它们在脑炎症过程中的重要作用。
Increased levels of prostanoids have been implicated in various neuropathological diseases, although little is known about their cellular sources inside the brain. In this study, we analyzed the expression of cyclooxygenase-2 (COX-2), a key enzyme in arachidonic acid metabolism, in rat microglia. COX-2 mRNA and protein as well as prostaglandin E(2) formation were almost undetectable in unstimulated microglial cultures but were found to be strongly upregulated in response to lipopolysaccharide. However, in contrast to most peripheral cells, proinflammatory cytokines such as tumor necrosis factor alpha, interleukin-1 beta or interleukin-6 failed to markedly induce COX-2 expression. Similar effects were observed by analyzing transcription nuclear factor-kappa B (NF-kappa B) which was strongly activated in microglia by lipopolysaccharide but not by incubation with cytokines. Moreover, known inhibitors of NF-kappa B activation, such as dexamethasone and the antioxidant pyrrolidine dithiocarbamate, as well as the protein kinase C (PKC) inhibitor Go6976, strongly reduced lipopolysaccharide-induced COX-2 transcription, indicating the involvement of NF-kappa B and PKC in COX-2 expression. Our results suggest that microglia may represent an important source of prostanoids in the brain, thus reinforcing their prominent role in cerebral inflammatory processes.