title: Hyperinduction of cyclooxygenase-2-mediated proinflammatory cascade: a mechanism for the pathogenesis of avian influenza H5N1 infection.
abstract: 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.
authors.affiliation: Department of Microbiology, Siriraj Hospital, Bangkok, Thailand.
authors.forename: Suki M Y
authors.initials: SM
authors.lastname: Lee
authors.forename: Chung-Yan
authors.initials: CY
authors.lastname: Cheung
authors.forename: John M
authors.initials: JM
authors.lastname: Nicholls
authors.forename: Kenrie P Y
authors.initials: KP
authors.lastname: Hui
authors.forename: Connie Y H
authors.initials: CY
authors.lastname: Leung
authors.forename: Mongkol
authors.initials: M
authors.lastname: Uiprasertkul
authors.forename: George L
authors.initials: GL
authors.lastname: Tipoe
authors.forename: Yu-Lung
authors.initials: YL
authors.lastname: Lau
authors.forename: Leo L M
authors.initials: LL
authors.lastname: Poon
authors.forename: Nancy Y
authors.initials: NY
authors.lastname: Ip
authors.forename: Yi
authors.initials: Y
authors.lastname: Guan
authors.forename: J S Malik
authors.initials: JS
authors.lastname: Peiris
mesh_terms: D000818:Animals; D001717:Birds; D051546:Cyclooxygenase 2 / Q000096:biosynthesis* / Q000235:genetics; D052246:Cyclooxygenase 2 Inhibitors; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity*; D005585:Influenza in Birds / Q000201:enzymology* / Q000276:immunology / Q000821:virology; D007251:Influenza, Human / Q000201:enzymology / Q000821:virology
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D051546:Cyclooxygenase 2