Hyperinduction of cyclooxygenase-2-mediated proinflammatory cascade: a mechanism for the pathogenesis of avian influenza H5N1 infection.
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.
Lee
Suki M Y
SM
Department of Microbiology, Siriraj Hospital, Bangkok, Thailand.
Cheung
Chung-Yan
CY
Nicholls
John M
JM
Hui
Kenrie P Y
KP
Leung
Connie Y H
CY
Uiprasertkul
Mongkol
M
Tipoe
George L
GL
Lau
Yu-Lung
YL
Poon
Leo L M
LL
Ip
Nancy Y
NY
Guan
Yi
Y
Peiris
J S Malik
JS
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
D052246:Cyclooxygenase 2 Inhibitors; D051546:Cyclooxygenase 2