Iron oxide nanoparticles modulate lipopolysaccharide-induced inflammatory responses in primary human monocytes

Susann Grosse,1 Jørgen Stenvik,1,2 Asbjørn M Nilsen1 1Department of Cancer Research and Molecular Medicine, 2Centre of Molecular Inflammation Research, Norwegian University of Science and Technology, Trondheim, Norway Abstract: Co-stimulation of the immune system to more than...

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Autores principales: Grosse S, Stenvik J, Nilsen AM
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Lenguaje:EN
Publicado: Dove Medical Press 2016
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spelling oai:doaj.org-article:ad1be379fee2400a8dcc70fb1e8949322021-12-02T02:42:30ZIron oxide nanoparticles modulate lipopolysaccharide-induced inflammatory responses in primary human monocytes1178-2013https://doaj.org/article/ad1be379fee2400a8dcc70fb1e8949322016-09-01T00:00:00Zhttps://www.dovepress.com/iron-oxide-nanoparticles-modulate-lipopolysaccharide-induced-inflammat-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Susann Grosse,1 Jørgen Stenvik,1,2 Asbjørn M Nilsen1 1Department of Cancer Research and Molecular Medicine, 2Centre of Molecular Inflammation Research, Norwegian University of Science and Technology, Trondheim, Norway Abstract: Co-stimulation of the immune system to more than one agent concomitantly is very common in real life, and considering the increasing use of engineered nanoparticles and nanomaterials, it is highly relevant to assess the ability of these materials to modulate key innate immune responses, which has not yet been studied in detail. We investigated the immunomodulatory effects of 10 nm and 30 nm iron oxide nanoparticles (IONPs) on primary human monocytes in the presence and absence of Toll-like receptor 4 agonist lipopolysaccharide (LPS). Prior to the cell studies, we characterized the physicochemical properties of the nanoparticles in cell culture medium and ensured that the nanoparticles were free from biological contamination. Cellular uptake of the IONPs in monocytes was assessed using transmission electron microscopy. Using enzyme-linked immunosorbent assay, we found that the IONPs per se did not induce the production of proinflammatory cytokines tumor necrosis factor-α, interleukin-6, and interleukin-1β. However, the IONPs had the ability to suppress LPS-induced nuclear factor kappa B activation and production of proinflammatory cytokines in primary human monocytes in an LPS and a particle dose-dependent manner. Using confocal microscopy and fluorescently labeled LPS, we showed that the effects correlated with impaired LPS internalization by monocytes in the presence of IONPs, which could be partly explained by LPS adsorption onto the nanoparticle surface. Additionally, the results from particle pretreatment experiments indicate that other cellular mechanisms might also play a role in the observed effects, which warrants further studies to elucidate the additional mechanisms underlying the capacity of IONPs to alter the reactivity of monocytes to LPS and to mount an appropriate cellular response. Keywords: iron oxide nanoparticles, primary human monocytes, PBMCs, cytokines, LPS adsorption, Toll-like receptorsGrosse SStenvik JNilsen AMDove Medical PressarticleIron oxide nanoparticlesprimary human monocyteslipopolysaccharideToll-like receptorsMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 11, Pp 4625-4642 (2016)
institution DOAJ
collection DOAJ
language EN
topic Iron oxide nanoparticles
primary human monocytes
lipopolysaccharide
Toll-like receptors
Medicine (General)
R5-920
spellingShingle Iron oxide nanoparticles
primary human monocytes
lipopolysaccharide
Toll-like receptors
Medicine (General)
R5-920
Grosse S
Stenvik J
Nilsen AM
Iron oxide nanoparticles modulate lipopolysaccharide-induced inflammatory responses in primary human monocytes
description Susann Grosse,1 Jørgen Stenvik,1,2 Asbjørn M Nilsen1 1Department of Cancer Research and Molecular Medicine, 2Centre of Molecular Inflammation Research, Norwegian University of Science and Technology, Trondheim, Norway Abstract: Co-stimulation of the immune system to more than one agent concomitantly is very common in real life, and considering the increasing use of engineered nanoparticles and nanomaterials, it is highly relevant to assess the ability of these materials to modulate key innate immune responses, which has not yet been studied in detail. We investigated the immunomodulatory effects of 10 nm and 30 nm iron oxide nanoparticles (IONPs) on primary human monocytes in the presence and absence of Toll-like receptor 4 agonist lipopolysaccharide (LPS). Prior to the cell studies, we characterized the physicochemical properties of the nanoparticles in cell culture medium and ensured that the nanoparticles were free from biological contamination. Cellular uptake of the IONPs in monocytes was assessed using transmission electron microscopy. Using enzyme-linked immunosorbent assay, we found that the IONPs per se did not induce the production of proinflammatory cytokines tumor necrosis factor-α, interleukin-6, and interleukin-1β. However, the IONPs had the ability to suppress LPS-induced nuclear factor kappa B activation and production of proinflammatory cytokines in primary human monocytes in an LPS and a particle dose-dependent manner. Using confocal microscopy and fluorescently labeled LPS, we showed that the effects correlated with impaired LPS internalization by monocytes in the presence of IONPs, which could be partly explained by LPS adsorption onto the nanoparticle surface. Additionally, the results from particle pretreatment experiments indicate that other cellular mechanisms might also play a role in the observed effects, which warrants further studies to elucidate the additional mechanisms underlying the capacity of IONPs to alter the reactivity of monocytes to LPS and to mount an appropriate cellular response. Keywords: iron oxide nanoparticles, primary human monocytes, PBMCs, cytokines, LPS adsorption, Toll-like receptors
format article
author Grosse S
Stenvik J
Nilsen AM
author_facet Grosse S
Stenvik J
Nilsen AM
author_sort Grosse S
title Iron oxide nanoparticles modulate lipopolysaccharide-induced inflammatory responses in primary human monocytes
title_short Iron oxide nanoparticles modulate lipopolysaccharide-induced inflammatory responses in primary human monocytes
title_full Iron oxide nanoparticles modulate lipopolysaccharide-induced inflammatory responses in primary human monocytes
title_fullStr Iron oxide nanoparticles modulate lipopolysaccharide-induced inflammatory responses in primary human monocytes
title_full_unstemmed Iron oxide nanoparticles modulate lipopolysaccharide-induced inflammatory responses in primary human monocytes
title_sort iron oxide nanoparticles modulate lipopolysaccharide-induced inflammatory responses in primary human monocytes
publisher Dove Medical Press
publishDate 2016
url https://doaj.org/article/ad1be379fee2400a8dcc70fb1e894932
work_keys_str_mv AT grosses ironoxidenanoparticlesmodulatelipopolysaccharideinducedinflammatoryresponsesinprimaryhumanmonocytes
AT stenvikj ironoxidenanoparticlesmodulatelipopolysaccharideinducedinflammatoryresponsesinprimaryhumanmonocytes
AT nilsenam ironoxidenanoparticlesmodulatelipopolysaccharideinducedinflammatoryresponsesinprimaryhumanmonocytes
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