Inhibition of mevalonate pathway by macrophage-specific delivery of atorvastatin prevents their pro-inflammatory polarisation.

atorvastatin glucan particles macrophage-specific delivery mevalonate pathway

Journal

Insect molecular biology
ISSN: 1365-2583
Titre abrégé: Insect Mol Biol
Pays: England
ID NLM: 9303579

Informations de publication

Date de publication:
17 Feb 2024
Historique:
received: 24 08 2023
accepted: 30 01 2024
medline: 17 2 2024
pubmed: 17 2 2024
entrez: 17 2 2024
Statut: aheadofprint

Résumé

Adjustment of the cellular metabolism of pro-inflammatory macrophages is essential for their bactericidal function; however, it underlies the development of many human diseases if induced chronically. Therefore, intervention of macrophage metabolic polarisation has been recognised as a potent strategy for their treatment. Although many small-molecule inhibitors affecting macrophage metabolism have been identified, their in vivo administration requires a tool for macrophage-specific delivery to limit their potential side effects. Here, we establish Drosophila melanogaster as a simple experimental model for in vivo testing of macrophage-specific delivery tools. We found that yeast-derived glucan particles (GPs) are suitable for macrophage-specific delivery of small-molecule inhibitors. Systemic administration of GPs loaded with atorvastatin, the inhibitor of hydroxy-methyl-glutaryl-CoA reductase (Hmgcr), leads to intervention of mevalonate pathway specifically in macrophages, without affecting HMGCR activity in other tissues. Using this tool, we demonstrate that mevalonate pathway is essential for macrophage pro-inflammatory polarisation and individual's survival of infection.

Identifiants

pubmed: 38367277
doi: 10.1111/imb.12900
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : Grantová Agentura České Republiky
ID : 19-26127X
Organisme : Grantová Agentura České Republiky
ID : 23-06133S
Organisme : Grantová Agentura České Republiky
ID : 20-14030S
Organisme : Technologická Agentura České Republiky
Organisme : USB Grant Agency
ID : 026/2021/P

Informations de copyright

© 2024 The Authors. Insect Molecular Biology published by John Wiley & Sons Ltd on behalf of Royal Entomological Society.

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Auteurs

Gabriela Krejčová (G)

Faculty of Science, Department of Molecular Biology and Genetics, University of South Bohemia, České Budějovice, Czech Republic.
Biology Centre CAS, Institute of Entomology, České Budějovice, Czech Republic.

Gabriela Ruphuy (G)

Department of Chemical Engineering, University of Chemistry and Technology Prague, Prague, Czech Republic.

Petra Šalamúnová (P)

Department of Chemical Engineering, University of Chemistry and Technology Prague, Prague, Czech Republic.

Erik Sonntag (E)

Department of Chemical Engineering, University of Chemistry and Technology Prague, Prague, Czech Republic.

František Štěpánek (F)

Department of Chemical Engineering, University of Chemistry and Technology Prague, Prague, Czech Republic.

Adam Bajgar (A)

Faculty of Science, Department of Molecular Biology and Genetics, University of South Bohemia, České Budějovice, Czech Republic.
Biology Centre CAS, Institute of Entomology, České Budějovice, Czech Republic.

Classifications MeSH