Hyperinduction of cyclooxygenase-2-mediated proinflammatory cascade: A mechanism for the pathogenesis of avian influenza H5N1 infection
Hyperinduction of cyclooxygenase-2-mediated proinflammatory cascade: A mechanism for the pathogenesis of avian influenza H5N1 infection
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DOI：
10.1086/590499
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发表时间：
2008-08-15
影响因子：
6.4
通讯作者：
Peiris, J. S. Malik
中科院分区：
文献类型：
--
作者：
Lee, Suki M. Y.;Cheung, Chung-Yan;Peiris, J. S. Malik
H5N1人感染的发病机制尚不清楚。本研究表明，环氧化酶-2 （COX-2）在体外H5N1感染的巨噬细胞和死于H5N1疾病的患者尸检中获得的肺组织样本的上皮细胞中被强烈诱导。新的研究结果表明，体外h5n1感染巨噬细胞的分泌因子可在上皮细胞中高诱导COX-2，以及肿瘤坏死因子α和其他促炎细胞因子。这种促炎反应的扩增是迅速的，由h5n1引发的促炎级联引起的影响比由直接病毒感染引起的影响更广泛。此外，选择性COX-2抑制剂抑制促炎级联中细胞因子的高诱导，表明COX-2在h5n1高诱导的宿主促炎级联中起调节作用。这些数据为可能开发用于治疗H5N1疾病的新型治疗干预措施（作为抗病毒药物的辅助手段）提供了基础。
The mechanism for the pathogenesis of H5N1 infection in humans remains unclear. This study reveals that cyclooxygenase-2 (COX-2) was strongly induced in H5N1-infected macrophages in vitro and in epithelial cells of lung tissue samples obtained during autopsy of patients who died of H5N1 disease. Novel findings demonstrated that COX-2, along with tumor necrosis factor alpha and other proinflammatory cytokines were hyperinduced in epithelial cells by secretory factors from H5N1-infected macrophages in vitro. This amplification of the proinflammatory response is rapid, and the effects elicited by the H5N1-triggered proinflammatory cascade are broader than those arising from direct viral infection. Furthermore, selective COX-2 inhibitors suppress the hyperinduction of cytokines in the proinflammatory cascade, indicating a regulatory role for COX-2 in the H5N1-hyperinduced host proinflammatory cascade. These data provide a basis for the possible development of novel therapeutic interventions for the treatment of H5N1 disease, as adjuncts to antiviral drugs.