Membrane fusogenic lysine type lipid assemblies possess enhanced NLRP3 inflammasome activation potency

Jieyan He, Tianshu Li, Tomasz Próchnicki, Gabor Horvath, Eicke Latz, Shinji Takeoka

Research output: Contribution to journalArticle

Abstract

Lysine (K) type cationic lipid with a propyl spacer and ditetradecyl hydrophobic moieties composing liposomes, K3C14, previously studied for gene delivery, were reported to activate the NLRP3 inflammasomes in human macrophages via the conventional phagolysosomal pathway. In this study, K3C16, a propyl spacer bearing lysine type lipids with dihexadecyl moieties (an extension of two hydrocarbon tail length) were compared with K3C14 as liposomes. Such a small change in tail length did not alter the physical properties such as size distribution, zeta potential and polydispersity index (PDI). The NLRP3 activation potency of K3C16 was shown to be 1.5-fold higher. Yet, the toxicity was minimal, whereas K3C14 has shown to cause significant cell death after 24 h incubation. Even in the presence of endocytosis inhibitors, cytochalasin D or dynasore, K3C16 continued to activate the NLRP3 inflammasomes and to induce IL-1β release. To our surprise, K3C16 liposomes were confirmed to fuse with the plasma membrane of human macrophages and CHO-K1 cells. It is demonstrated that the change in hydrophobic tail length by two hydrocarbons drastically changed a cellular entry route and potency in activating the NLRP3 inflammasomes.

Original languageEnglish
Article number100623
JournalBiochemistry and Biophysics Reports
Volume18
DOIs
Publication statusPublished - 2019 Jul 1

Fingerprint

Inflammasomes
Liposomes
Lysine
Tail
Macrophages
Chemical activation
Hydrocarbons
Membranes
Lipids
Bearings (structural)
Cytochalasin D
CHO Cells
Polydispersity
Electric fuses
Cell death
Zeta potential
Cell membranes
Endocytosis
Interleukin-1
Toxicity

Keywords

  • Cationic liposome
  • Endocytosis
  • IL-1β
  • Lysine
  • Membrane fusion
  • NLRP3 inflammasome

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Membrane fusogenic lysine type lipid assemblies possess enhanced NLRP3 inflammasome activation potency. / He, Jieyan; Li, Tianshu; Próchnicki, Tomasz; Horvath, Gabor; Latz, Eicke; Takeoka, Shinji.

In: Biochemistry and Biophysics Reports, Vol. 18, 100623, 01.07.2019.

Research output: Contribution to journalArticle

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AU - Takeoka, Shinji

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