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

Autor: 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., Ruphuy G; Department of Chemical Engineering, University of Chemistry and Technology Prague, Prague, Czech Republic., Šalamúnová P; Department of Chemical Engineering, University of Chemistry and Technology Prague, Prague, Czech Republic., Sonntag E; Department of Chemical Engineering, University of Chemistry and Technology Prague, Prague, Czech Republic., Štěpánek F; Department of Chemical Engineering, University of Chemistry and Technology Prague, Prague, Czech Republic., 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.
Jazyk: angličtina
Zdroj: Insect molecular biology [Insect Mol Biol] 2024 Aug; Vol. 33 (4), pp. 323-337. Date of Electronic Publication: 2024 Feb 17.
DOI: 10.1111/imb.12900
Abstrakt: 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.
(© 2024 The Authors. Insect Molecular Biology published by John Wiley & Sons Ltd on behalf of Royal Entomological Society.)
Databáze: MEDLINE
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