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Sarcoidosis exosomes stimulate monocytes to produce pro-inflammatory cytokines and CCL2

Pulmonary sarcoidosis has unknown etiology, a difficult diagnostic procedure and no curative treatment. Extracellular vesicles including exosomes are nano-sized entities released from all cell types. Previous studies of exosomes from bronchoalveolar lavage fluid (BALF) of sarcoidosis patients have r...

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Autores principales: Wahlund, Casper J. E., Gucluler Akpinar, Gozde, Steiner, Loïc, Ibrahim, Ahmed, Bandeira, Elga, Lepzien, Rico, Lukic, Ana, Smed-Sörensen, Anna, Kullberg, Susanna, Eklund, Anders, Grunewald, Johan, Gabrielsson, Susanne
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7501276/
https://www.ncbi.nlm.nih.gov/pubmed/32948789
http://dx.doi.org/10.1038/s41598-020-72067-7
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author Wahlund, Casper J. E.
Gucluler Akpinar, Gozde
Steiner, Loïc
Ibrahim, Ahmed
Bandeira, Elga
Lepzien, Rico
Lukic, Ana
Smed-Sörensen, Anna
Kullberg, Susanna
Eklund, Anders
Grunewald, Johan
Gabrielsson, Susanne
author_facet Wahlund, Casper J. E.
Gucluler Akpinar, Gozde
Steiner, Loïc
Ibrahim, Ahmed
Bandeira, Elga
Lepzien, Rico
Lukic, Ana
Smed-Sörensen, Anna
Kullberg, Susanna
Eklund, Anders
Grunewald, Johan
Gabrielsson, Susanne
author_sort Wahlund, Casper J. E.
collection PubMed
description Pulmonary sarcoidosis has unknown etiology, a difficult diagnostic procedure and no curative treatment. Extracellular vesicles including exosomes are nano-sized entities released from all cell types. Previous studies of exosomes from bronchoalveolar lavage fluid (BALF) of sarcoidosis patients have revealed pro-inflammatory components and abilities, but cell sources and mechanisms have not been identified. In the current study, we found that BALF exosomes from sarcoidosis patients, but not from healthy individuals, induced a dose-dependent elevation of intracellular IL-1β in monocytes. Analyses of supernatants showed that patient exosomes also induced release of IL-1β, IL-6 and TNF from both PBMCs and enriched monocytes, suggesting that the observed effect is direct on monocytes. The potently chemotactic chemokine CCL2 was induced by exosomes from a subgroup of patients, and in a blocking assay the exosome-induced CCL2 was reduced for 13 out of 19 patients by the asthma drug Montelukast, a cysteinyl leukotriene receptor antagonist. Further, reactive oxygen species generation by PBMCs was induced to a higher degree by patient exosomes compared to healthy exosomes. These findings add to an emerging picture of exosomes as mediators and disseminators of inflammation, and open for further investigations of the link between CCL2 and exosomal leukotrienes in sarcoidosis.
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spelling pubmed-75012762020-09-22 Sarcoidosis exosomes stimulate monocytes to produce pro-inflammatory cytokines and CCL2 Wahlund, Casper J. E. Gucluler Akpinar, Gozde Steiner, Loïc Ibrahim, Ahmed Bandeira, Elga Lepzien, Rico Lukic, Ana Smed-Sörensen, Anna Kullberg, Susanna Eklund, Anders Grunewald, Johan Gabrielsson, Susanne Sci Rep Article Pulmonary sarcoidosis has unknown etiology, a difficult diagnostic procedure and no curative treatment. Extracellular vesicles including exosomes are nano-sized entities released from all cell types. Previous studies of exosomes from bronchoalveolar lavage fluid (BALF) of sarcoidosis patients have revealed pro-inflammatory components and abilities, but cell sources and mechanisms have not been identified. In the current study, we found that BALF exosomes from sarcoidosis patients, but not from healthy individuals, induced a dose-dependent elevation of intracellular IL-1β in monocytes. Analyses of supernatants showed that patient exosomes also induced release of IL-1β, IL-6 and TNF from both PBMCs and enriched monocytes, suggesting that the observed effect is direct on monocytes. The potently chemotactic chemokine CCL2 was induced by exosomes from a subgroup of patients, and in a blocking assay the exosome-induced CCL2 was reduced for 13 out of 19 patients by the asthma drug Montelukast, a cysteinyl leukotriene receptor antagonist. Further, reactive oxygen species generation by PBMCs was induced to a higher degree by patient exosomes compared to healthy exosomes. These findings add to an emerging picture of exosomes as mediators and disseminators of inflammation, and open for further investigations of the link between CCL2 and exosomal leukotrienes in sarcoidosis. Nature Publishing Group UK 2020-09-18 /pmc/articles/PMC7501276/ /pubmed/32948789 http://dx.doi.org/10.1038/s41598-020-72067-7 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Wahlund, Casper J. E.
Gucluler Akpinar, Gozde
Steiner, Loïc
Ibrahim, Ahmed
Bandeira, Elga
Lepzien, Rico
Lukic, Ana
Smed-Sörensen, Anna
Kullberg, Susanna
Eklund, Anders
Grunewald, Johan
Gabrielsson, Susanne
Sarcoidosis exosomes stimulate monocytes to produce pro-inflammatory cytokines and CCL2
title Sarcoidosis exosomes stimulate monocytes to produce pro-inflammatory cytokines and CCL2
title_full Sarcoidosis exosomes stimulate monocytes to produce pro-inflammatory cytokines and CCL2
title_fullStr Sarcoidosis exosomes stimulate monocytes to produce pro-inflammatory cytokines and CCL2
title_full_unstemmed Sarcoidosis exosomes stimulate monocytes to produce pro-inflammatory cytokines and CCL2
title_short Sarcoidosis exosomes stimulate monocytes to produce pro-inflammatory cytokines and CCL2
title_sort sarcoidosis exosomes stimulate monocytes to produce pro-inflammatory cytokines and ccl2
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7501276/
https://www.ncbi.nlm.nih.gov/pubmed/32948789
http://dx.doi.org/10.1038/s41598-020-72067-7
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