Hyperinduction of cyclooxygenase-2-mediated proinflammatory cascade: a mechanism for the pathogenesis of avian influenza H5N1 infection.

Suki M Y Lee 1 Chung-Yan Cheung 1 John M Nicholls 2 Kenrie P Y Hui 1 Connie y H Leung 1 Mongkol Uiprasertkul 3 George L Tipoe 4 Yu-Lung Lau 5 Leo L M Poon 1 Nancy Y Ip 1 Yi Guan 6 J S Malik Peiris 1, 7, *
* Corresponding author
1 Department of Microbiology [HKU]
2 Department of pathology [HKU]
3 Department of Pathology Siriraj Hospital
4 Department of Anatomy [HKU]
5 Department of Paediatrics and Adolescent Medicine [HKU]
6 Department of Biochemistry
7 Centre de recherche Université de Hong-Kong-Pasteur
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.
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Suki M Y Lee, Chung-Yan Cheung, John M Nicholls, Kenrie P Y Hui, Connie y H Leung, et al.. Hyperinduction of cyclooxygenase-2-mediated proinflammatory cascade: a mechanism for the pathogenesis of avian influenza H5N1 infection.. Journal of Infectious Diseases, Oxford University Press (OUP), 2008, 198 (4), pp.525-35. ⟨10.1086/590499⟩. ⟨pasteur-00588953⟩

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