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Folate Receptor Expression by Human Monocyte–Derived Macrophage Subtypes and Effects of Corticosteroids

OBJECTIVE: Folate receptor beta (FR-β) has been used as a clinical marker and target in multiple inflammatory diseases, including osteoarthritis (OA) and rheumatoid arthritis (RA). However, the conditions under which FR-β(+) macrophages arise remain unclear and could be affected by corticosteroids....

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Autores principales: Warmink, Kelly, Siebelt, Michiel, Low, Philip S., Riemers, Frank M., Wang, Bingbing, Plomp, Saskia G. M., Tryfonidou, Marianna A., van Weeren, P. René, Weinans, Harrie, Korthagen, Nicoline M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9137314/
https://www.ncbi.nlm.nih.gov/pubmed/35255727
http://dx.doi.org/10.1177/19476035221081469
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author Warmink, Kelly
Siebelt, Michiel
Low, Philip S.
Riemers, Frank M.
Wang, Bingbing
Plomp, Saskia G. M.
Tryfonidou, Marianna A.
van Weeren, P. René
Weinans, Harrie
Korthagen, Nicoline M.
author_facet Warmink, Kelly
Siebelt, Michiel
Low, Philip S.
Riemers, Frank M.
Wang, Bingbing
Plomp, Saskia G. M.
Tryfonidou, Marianna A.
van Weeren, P. René
Weinans, Harrie
Korthagen, Nicoline M.
author_sort Warmink, Kelly
collection PubMed
description OBJECTIVE: Folate receptor beta (FR-β) has been used as a clinical marker and target in multiple inflammatory diseases, including osteoarthritis (OA) and rheumatoid arthritis (RA). However, the conditions under which FR-β(+) macrophages arise remain unclear and could be affected by corticosteroids. Therefore, we studied FR-β expression in vitro in macrophage subtypes and determined their response to triamcinolone acetonide (TA), a clinically often-used corticosteroid. DESIGN: Human monocyte–derived macrophages were differentiated to the known M0, M1, or M2 macrophage phenotypes. The phenotype and FR-β expression and plasticity of the macrophage subtypes were determined using flow cytometry, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and enzyme-linked immunosorbent assay (ELISA). RESULTS: FR-β expression was low in granulocyte-macrophage colony-stimulating factor (GM-CSF)-generated (M1-like) macrophages and high in macrophage colony-stimulating factor (M-CSF)-generated (M0 and M2-like) macrophages. FR-β expression remained high once the M0 or M2 macrophages were stimulated with pro-inflammatory stimuli (interferon-γ plus lipopolysaccharide) to induce M1-like macrophages. On the contrary, anti-inflammatory TA treatment skewed GM-CSF macrophage differentiation toward an M2 and FR-β(+) phenotype. CONCLUSIONS: As corticosteroids skewed monocytes toward an FR-β-expressing, anti-inflammatory phenotype, even in an M1 priming GM-CSF environment, FR-β has potential as a biomarker to monitor success of treatment with corticosteroids. Without corticosteroid treatment, M-CSF alone induces high FR-β expression which remains high under pro-inflammatory conditions. This explains why pro-inflammatory FR-β(+) macrophages (exposed to M-CSF) are observed in arthritis patients and correlate with disease severity.
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spelling pubmed-91373142022-06-08 Folate Receptor Expression by Human Monocyte–Derived Macrophage Subtypes and Effects of Corticosteroids Warmink, Kelly Siebelt, Michiel Low, Philip S. Riemers, Frank M. Wang, Bingbing Plomp, Saskia G. M. Tryfonidou, Marianna A. van Weeren, P. René Weinans, Harrie Korthagen, Nicoline M. Cartilage Basic Research Article OBJECTIVE: Folate receptor beta (FR-β) has been used as a clinical marker and target in multiple inflammatory diseases, including osteoarthritis (OA) and rheumatoid arthritis (RA). However, the conditions under which FR-β(+) macrophages arise remain unclear and could be affected by corticosteroids. Therefore, we studied FR-β expression in vitro in macrophage subtypes and determined their response to triamcinolone acetonide (TA), a clinically often-used corticosteroid. DESIGN: Human monocyte–derived macrophages were differentiated to the known M0, M1, or M2 macrophage phenotypes. The phenotype and FR-β expression and plasticity of the macrophage subtypes were determined using flow cytometry, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and enzyme-linked immunosorbent assay (ELISA). RESULTS: FR-β expression was low in granulocyte-macrophage colony-stimulating factor (GM-CSF)-generated (M1-like) macrophages and high in macrophage colony-stimulating factor (M-CSF)-generated (M0 and M2-like) macrophages. FR-β expression remained high once the M0 or M2 macrophages were stimulated with pro-inflammatory stimuli (interferon-γ plus lipopolysaccharide) to induce M1-like macrophages. On the contrary, anti-inflammatory TA treatment skewed GM-CSF macrophage differentiation toward an M2 and FR-β(+) phenotype. CONCLUSIONS: As corticosteroids skewed monocytes toward an FR-β-expressing, anti-inflammatory phenotype, even in an M1 priming GM-CSF environment, FR-β has potential as a biomarker to monitor success of treatment with corticosteroids. Without corticosteroid treatment, M-CSF alone induces high FR-β expression which remains high under pro-inflammatory conditions. This explains why pro-inflammatory FR-β(+) macrophages (exposed to M-CSF) are observed in arthritis patients and correlate with disease severity. SAGE Publications 2022-03-07 /pmc/articles/PMC9137314/ /pubmed/35255727 http://dx.doi.org/10.1177/19476035221081469 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution 4.0 License (https://creativecommons.org/licenses/by/4.0/) which permits any use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).
spellingShingle Basic Research Article
Warmink, Kelly
Siebelt, Michiel
Low, Philip S.
Riemers, Frank M.
Wang, Bingbing
Plomp, Saskia G. M.
Tryfonidou, Marianna A.
van Weeren, P. René
Weinans, Harrie
Korthagen, Nicoline M.
Folate Receptor Expression by Human Monocyte–Derived Macrophage Subtypes and Effects of Corticosteroids
title Folate Receptor Expression by Human Monocyte–Derived Macrophage Subtypes and Effects of Corticosteroids
title_full Folate Receptor Expression by Human Monocyte–Derived Macrophage Subtypes and Effects of Corticosteroids
title_fullStr Folate Receptor Expression by Human Monocyte–Derived Macrophage Subtypes and Effects of Corticosteroids
title_full_unstemmed Folate Receptor Expression by Human Monocyte–Derived Macrophage Subtypes and Effects of Corticosteroids
title_short Folate Receptor Expression by Human Monocyte–Derived Macrophage Subtypes and Effects of Corticosteroids
title_sort folate receptor expression by human monocyte–derived macrophage subtypes and effects of corticosteroids
topic Basic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9137314/
https://www.ncbi.nlm.nih.gov/pubmed/35255727
http://dx.doi.org/10.1177/19476035221081469
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