Traffic-related diesel pollution acparticles impair the lysosomal functions of human iPSC-derived microglia

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378041%3A_____%2F25%3A00635869" target="_blank" >RIV/68378041:_____/25:00635869 - isvavai.cz</a>

Výsledek na webu

<a href="https://www.sciencedirect.com/science/article/pii/S0160412025002181?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0160412025002181?via%3Dihub</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.envint.2025.109467" target="_blank" >10.1016/j.envint.2025.109467</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Traffic-related diesel pollution acparticles impair the lysosomal functions of human iPSC-derived microglia

Popis výsledku v původním jazyce

Exposure to air pollution is associated with neurological diseases. Traffic is a major source of air pollution, consisting of a complex mixture of ultrafine particles, that can invade the brain and induce a microglia-mediated inflammatory response. However, the exact mechanisms of how traffic-related particles impact human microglia remain poorly understood. This study investigates the effects of diesel exhaust particles (DEPs) on human induced pluripotent stem cell-derived microglia-like cells (iMGL). We exposed iMGLs to three different DEPs and studied the impact on the iMGL transcriptome and functionality, focusing on cytokine secretion, mitochondrial respiration, lysosomal function, and phagocytosis. A20 particles were collected from a heavy-duty engine run with petroleum diesel. For A0, the same engine was run with renewable diesel. E6 was produced with a modern 2019 model diesel passenger car run with renewable diesel. RNAseq revealed activation of the cytokine storm pathway and inhibition of the autophagy pathway in iMGLs after exposure to particles derived from older diesel emission technology (A20, A0). Particles from the modern diesel engine technology (E6) did not alter microglial transcriptome after 24 h exposure. A20 and A0 exposure led to impaired lysosomal functions in iMGLs. In contrast, E6 did not cause major alterations in microglia functions. In addition, we show that response to particles is more pronounced in human iMGLs compared to mouse primary microglia. To conclude, particles from older emission technology impair phago-lysosomal functions of iMGLs, but modern alternatives with filtration do not induce drastic changes in the functionality of iMGLs.

Název v anglickém jazyce

Traffic-related diesel pollution acparticles impair the lysosomal functions of human iPSC-derived microglia

Popis výsledku anglicky

Exposure to air pollution is associated with neurological diseases. Traffic is a major source of air pollution, consisting of a complex mixture of ultrafine particles, that can invade the brain and induce a microglia-mediated inflammatory response. However, the exact mechanisms of how traffic-related particles impact human microglia remain poorly understood. This study investigates the effects of diesel exhaust particles (DEPs) on human induced pluripotent stem cell-derived microglia-like cells (iMGL). We exposed iMGLs to three different DEPs and studied the impact on the iMGL transcriptome and functionality, focusing on cytokine secretion, mitochondrial respiration, lysosomal function, and phagocytosis. A20 particles were collected from a heavy-duty engine run with petroleum diesel. For A0, the same engine was run with renewable diesel. E6 was produced with a modern 2019 model diesel passenger car run with renewable diesel. RNAseq revealed activation of the cytokine storm pathway and inhibition of the autophagy pathway in iMGLs after exposure to particles derived from older diesel emission technology (A20, A0). Particles from the modern diesel engine technology (E6) did not alter microglial transcriptome after 24 h exposure. A20 and A0 exposure led to impaired lysosomal functions in iMGLs. In contrast, E6 did not cause major alterations in microglia functions. In addition, we show that response to particles is more pronounced in human iMGLs compared to mouse primary microglia. To conclude, particles from older emission technology impair phago-lysosomal functions of iMGLs, but modern alternatives with filtration do not induce drastic changes in the functionality of iMGLs.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30108 - Toxicology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2025

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Environment International

ISSN

0160-4120

e-ISSN

1873-6750

Svazek periodika

199

Číslo periodika v rámci svazku

May

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

20

Strana od-do

109467

Kód UT WoS článku

001493909500001

EID výsledku v databázi Scopus

2-s2.0-105004552541