Cholesterol loading suppresses the atheroinflammatory gene polarization of human macrophages induced by colony stimulating factors

Abstract In atherosclerotic lesions, blood-derived monocytes differentiate into distinct macrophage subpopulations, and further into cholesterol-filled foam cells under a complex milieu of cytokines, which also contains macrophage-colony stimulating factor (M-CSF) and granulocyte–macrophage-colony s...

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Autores principales:	Jani Lappalainen, Nicolas Yeung, Su D. Nguyen, Matti Jauhiainen, Petri T. Kovanen, Miriam Lee-Rueckert
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d024a2c8f799481abd06e448627a9d01
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spelling	oai:doaj.org-article:d024a2c8f799481abd06e448627a9d012021-12-02T11:37:22ZCholesterol loading suppresses the atheroinflammatory gene polarization of human macrophages induced by colony stimulating factors10.1038/s41598-021-84249-y2045-2322https://doaj.org/article/d024a2c8f799481abd06e448627a9d012021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-84249-yhttps://doaj.org/toc/2045-2322Abstract In atherosclerotic lesions, blood-derived monocytes differentiate into distinct macrophage subpopulations, and further into cholesterol-filled foam cells under a complex milieu of cytokines, which also contains macrophage-colony stimulating factor (M-CSF) and granulocyte–macrophage-colony stimulating factor (GM-CSF). Here we generated human macrophages in the presence of either M-CSF or GM-CSF to obtain M-MØ and GM-MØ, respectively. The macrophages were converted into cholesterol-loaded foam cells by incubating them with acetyl-LDL, and their atheroinflammatory gene expression profiles were then assessed. Compared with GM-MØ, the M-MØ expressed higher levels of CD36, SRA1, and ACAT1, and also exhibited a greater ability to take up acetyl-LDL, esterify cholesterol, and become converted to foam cells. M-MØ foam cells expressed higher levels of ABCA1 and ABCG1, and, correspondingly, exhibited higher rates of cholesterol efflux to apoA-I and HDL2. Cholesterol loading of M-MØ strongly suppressed the high baseline expression of CCL2, whereas in GM-MØ the low baseline expression CCL2 remained unchanged during cholesterol loading. The expression of TNFA, IL1B, and CXCL8 were reduced in LPS-activated macrophage foam cells of either subtype. In summary, cholesterol loading converged the CSF-dependent expression of key genes related to intracellular cholesterol balance and inflammation. These findings suggest that transformation of CSF-polarized macrophages into foam cells may reduce their atheroinflammatory potential in atherogenesis.Jani LappalainenNicolas YeungSu D. NguyenMatti JauhiainenPetri T. KovanenMiriam Lee-RueckertNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-16 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jani Lappalainen Nicolas Yeung Su D. Nguyen Matti Jauhiainen Petri T. Kovanen Miriam Lee-Rueckert Cholesterol loading suppresses the atheroinflammatory gene polarization of human macrophages induced by colony stimulating factors
description	Abstract In atherosclerotic lesions, blood-derived monocytes differentiate into distinct macrophage subpopulations, and further into cholesterol-filled foam cells under a complex milieu of cytokines, which also contains macrophage-colony stimulating factor (M-CSF) and granulocyte–macrophage-colony stimulating factor (GM-CSF). Here we generated human macrophages in the presence of either M-CSF or GM-CSF to obtain M-MØ and GM-MØ, respectively. The macrophages were converted into cholesterol-loaded foam cells by incubating them with acetyl-LDL, and their atheroinflammatory gene expression profiles were then assessed. Compared with GM-MØ, the M-MØ expressed higher levels of CD36, SRA1, and ACAT1, and also exhibited a greater ability to take up acetyl-LDL, esterify cholesterol, and become converted to foam cells. M-MØ foam cells expressed higher levels of ABCA1 and ABCG1, and, correspondingly, exhibited higher rates of cholesterol efflux to apoA-I and HDL2. Cholesterol loading of M-MØ strongly suppressed the high baseline expression of CCL2, whereas in GM-MØ the low baseline expression CCL2 remained unchanged during cholesterol loading. The expression of TNFA, IL1B, and CXCL8 were reduced in LPS-activated macrophage foam cells of either subtype. In summary, cholesterol loading converged the CSF-dependent expression of key genes related to intracellular cholesterol balance and inflammation. These findings suggest that transformation of CSF-polarized macrophages into foam cells may reduce their atheroinflammatory potential in atherogenesis.
format	article
author	Jani Lappalainen Nicolas Yeung Su D. Nguyen Matti Jauhiainen Petri T. Kovanen Miriam Lee-Rueckert
author_facet	Jani Lappalainen Nicolas Yeung Su D. Nguyen Matti Jauhiainen Petri T. Kovanen Miriam Lee-Rueckert
author_sort	Jani Lappalainen
title	Cholesterol loading suppresses the atheroinflammatory gene polarization of human macrophages induced by colony stimulating factors
title_short	Cholesterol loading suppresses the atheroinflammatory gene polarization of human macrophages induced by colony stimulating factors
title_full	Cholesterol loading suppresses the atheroinflammatory gene polarization of human macrophages induced by colony stimulating factors
title_fullStr	Cholesterol loading suppresses the atheroinflammatory gene polarization of human macrophages induced by colony stimulating factors
title_full_unstemmed	Cholesterol loading suppresses the atheroinflammatory gene polarization of human macrophages induced by colony stimulating factors
title_sort	cholesterol loading suppresses the atheroinflammatory gene polarization of human macrophages induced by colony stimulating factors
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/d024a2c8f799481abd06e448627a9d01
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Cholesterol loading suppresses the atheroinflammatory gene polarization of human macrophages induced by colony stimulating factors

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