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

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60077344%3A_____%2F24%3A00583498" target="_blank" >RIV/60077344:_____/24:00583498 - isvavai.cz</a>
Alternative codes found
RIV/60076658:12310/24:43908881 RIV/60461373:22340/24:43930876
Result on the web
<a href="https://resjournals.onlinelibrary.wiley.com/doi/epdf/10.1111/imb.12900" target="_blank" >https://resjournals.onlinelibrary.wiley.com/doi/epdf/10.1111/imb.12900</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1111/imb.12900" target="_blank" >10.1111/imb.12900</a>

Result language
angličtina
Original language name
Inhibition of mevalonate pathway by macrophage-specific delivery of atorvastatin prevents their pro-inflammatory polarisation
Original language description
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.
Czech name
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Czech description
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Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10605 - Developmental biology

Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year
2024
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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