Pyroptosis in macrophages infected with dengue virus

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Pyroptosis in macrophages infected with dengue virus

 

Author: Cheung, Wing Hong Eddie
Title: Pyroptosis in macrophages infected with dengue virus
Degree: M.Sc.
Year: 2013
Subject: Macrophages.
Dengue viruses.
Hong Kong Polytechnic University -- Dissertations
Department: Dept. of Health Technology and Informatics
Pages: xiv, 73 leaves : ill. ; 30 cm.
Language: English
InnoPac Record: http://library.polyu.edu.hk/record=b2637243
URI: http://theses.lib.polyu.edu.hk/handle/200/7068
Abstract: Background: Dengue fever is a mosquito-borne disease and caused by dengue virus which is a member of the family Flaviviridae. During viral infection, macrophages are considered as the target cell for supporting viral replication. Pyroptosis may occur in macrophages in response to the dengue virus infection as an antiviral immunity. However, the molecular mechanism of pyroptosis in macrophages during dengue virus infection is still unclear. Aim: In the present study, human primary macrophages were infected by dengue virus and analyzed for activation of caspase-1, cytokines IL-1β, IL-18, apoptosis-associated speck-like protein (ASC), NALP3 and cell death using RT-PCR and ELISA. Results: Expression of mRNA for ASC, caspase-1, IL-1β and IL-18 were up-regulated after dengue virus infection. In addition, increased level of IL-1β was also demonstrated. However, IL-18 protein was not elevated after dengue virus infection. The present results indicated that mRNA expression of the members of the pyroptotic pathway and production of proinflammatory cytokine may be induced upon dengue virus infection. This study also examined the role of NALP3 inflammasome in triggering of caspase-1 activity. Up-regulation of NALP3 demonstrated that it played a role in the activation of caspase-1. Furthermore, the percentage of cell viability between infected and uninfected cells indicates that death of primary macrophages was enhanced by dengue virus infection. Conclusion: The combination of up-regulated NALP3, ASC, caspase-1, IL-1β and IL-18 genes, cell lysis, and secretion of IL-1β suggests that dengue virus infection may induce activation of caspase-1 via recognition of NALP3 to produce IL-1β leading to pyroptosis in primary macrophages.

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