Respiratory syncytial virus (RSV) infection induces cyclooxygenase 2: A potential target for RSV therapy
Respiratory syncytial virus (RSV) infection induces cyclooxygenase 2: A potential target for RSV therapy
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DOI：
10.4049/jimmunol.174.7.4356
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发表时间：
2005-04-01
影响因子：
4.4
通讯作者：
Blanco, JCG
中科院分区：
文献类型：
--
作者：
Richardson, JY;Ottolini, MG;Blanco, JCG
环氧合酶（cox）是一种限速酶，可启动花生四烯酸向前列腺素的转化。COX-2是被促炎剂上调的诱导异构体，启动许多前列腺素介导的炎症病理方面。环加氧酶及其产物pg在呼吸道合胞病毒（RSV）感染中的作用尚未得到评价。在这项研究中，我们证明了COX-2是由RSV感染人肺泡上皮细胞诱导的，同时产生pg。COX-2诱导与病毒剂量和感染后时间有关。cox -2特异性抑制剂NS-398和泛cox抑制剂吲哚美辛优先抑制PG的产生，而cox -1特异性抑制剂SC-560则没有作用。在体内，感染RSV的棉花大鼠的肺和细支气管肺泡灌洗细胞强烈诱导COX-2 mRNA的表达和蛋白的产生。体内COX-2在肺中的表达模式是周期性的，在第5天达到最终峰值，与最大的组织病理学相关。吲哚美辛治疗棉花大鼠可显著减轻RSV引起的肺组织病理变化。本研究中描述的研究首次证明COX-2是rsv诱导疾病的潜在治疗靶点。
Cyclooxygenases (COXs) are rate-limiting enzymes that initiate the conversion of arachidonic acid to prostanoids. COX-2 is the inducible isoform that is up-regulated by proinflammatory agents, initiating many prostanoid-mediated pathological aspects of inflammation. The roles of cyclooxygenases and their products, PGs, have not been evaluated during respiratory syncytial virus (RSV) infection. In this study we demonstrate that COX-2 is induced by RSV infection of human lung alveolar epithelial cells with the concomitant production of PGs. COX-2 induction was dependent on the dose of virus and the time postinfection. PG production was inhibited preferentially by NS-398, a COX-2-specific inhibitor, and indomethacin, a pan-COX inhibitor, but not by SC-560, a COX-1-specific inhibitor. In vivo, COX-2 mRNA expression and protein production were strongly induced in the lungs and cells derived from bronchioalveolar lavage of cotton rats infected with RSV. The pattern of COX-2 expression in vivo in lungs is cyclical, with a final peak on day 5 that correlates with maximal histopathology. Treatment of cotton rats with indomethacin significantly mitigated lung histopathology produced by RSV. The studies described in this study provide the first evidence that COX-2 is a potential therapeutic target in RSV-induced disease.