Author: Shrestha, Ashish C.; Wijesundara, Danushka K.; Masavuli, Makutiro G.; Mekonnen, Zelalem A.; Gowans, Eric J.; Grubor-Bauk, Branka
Title: Cytolytic Perforin as an Adjuvant to Enhance the Immunogenicity of DNA Vaccines Document date: 2019_4_30
ID: 141u6ax7_28
Snippet: Necrosis is considered as the mechanism of cell death by PRF as evidenced by release of lactate dehydrogenase (LDH) and low caspase activity [55, 56, 94] . LDH release occurs after the rupture of cell membrane during secondary necrosis [98, 99] . In contrast, LDH was not released by cells treated with doxorubicin (a proapoptotic drug) or cells transfected with NS3 wild type PRF or NS3 12del483A PRF (mutant and nontoxic PRF) [94] . Expression of P.....
Document: Necrosis is considered as the mechanism of cell death by PRF as evidenced by release of lactate dehydrogenase (LDH) and low caspase activity [55, 56, 94] . LDH release occurs after the rupture of cell membrane during secondary necrosis [98, 99] . In contrast, LDH was not released by cells treated with doxorubicin (a proapoptotic drug) or cells transfected with NS3 wild type PRF or NS3 12del483A PRF (mutant and nontoxic PRF) [94] . Expression of PRF from a cytolytic DNA, e.g., NS3 PRF vaccine, thus results in necrotic cell death mediated by receptor-interacting protein-1 kinase activity, as evidenced by detection of uncleaved cytokeratin 18 in Huh-7 cells [56] . Necrosis releases damage associated molecular patterns (DAMPs) which in turn activate DCs to migrate to the site of vaccination [100, 101] .
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