Inflammasome induction and immunostimulatory effects of CpG-ODN loaded liposomes containing DC-cholesterol

Date
2013
Authors
Bayyurt, B.
Gürsel I.
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Instructor
Source Title
Turkish Journal of Immunology
Print ISSN
1301109X
Electronic ISSN
Publisher
Turkish Society of Immunology
Volume
2
Issue
2
Pages
21 - 28
Language
Turkish
Type
Article
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Abstract

Objectives: This study aims to investigate the effects of cholesterol content and cationic property of liposomes on immune response. Materials and methods: Liposomes containing high amounts of 3β-[N-(N',N'-dimethylaminoethane)-carbamoyl] cholesterol hydrochloride (DC-cholesterol) were prepared and loaded with K- and D-type CpG oligonucleotide (CpG-ODN) via dehydration-rehydration (DRV) method. After splenocytes and peritoneal exudate cells (PECs) primed with lipopolysaccharide (LPS) was incubated either with free or liposomal CpG-ODN counterparts, supernatants were collected and used in cytokine (IFN-g, IL-1γ and IL-1β) ELISA. Additionally, supernatants of PECs primed with LPS and stimulated with liposomes containing different doses of DC-cholesterol were collected and used in IL-1β ELISA assay. Results: Low-dose CpG-ODN loaded liposomal formulations induced higher immune activation than free CpG-ODN at the same dose. While high-dose liposomal CpG-ODN formulations decreased pro-inflammatory cytokine production in splenocytes, they increased the secretion of IL-1β. Inflammasome activation was increased in a dose dependent manner when PECs primed with LPS were incubated with only liposomes. Varying lipid molar ratios of DC-Cholesterol containing liposomes increased IL-1β production based on increasing lipid molar ratio. Conclusion: This study revealed that type and lipid ratio of liposomes may alter the cellular efficacy of the loaded immune-stimulatory agent and may initiate inflammasome activation. © 2014 Turkish Journal of Immunology.

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Keywords
CpG-ODN, DC-cholesterol, Immune response, Inflammasome, Liposome, 3 beta [n [ n',n' dimethylaminoethane] caramoyl]cholesterol hydrochloride, cationic liposome, CpG oligodeoxynucleotide, gamma interferon, inflammasome, interleukin 12, interleukin 1beta, lipopolysaccharide, liposome, unclassified drug, Article, cholesterol synthesis, cytokine release, dehydration, enzyme linked immunosorbent assay, human, immune response, immunostimulation, peritoneal exudate cell, rehydration, spleen cell, supernatant
Citation
Published Version (Please cite this version)