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Polyethylene Glycol 35 (PEG35) Modulates Exosomal Uptake and Function

Polyethylene glycols (PEGs) are neutral polymers widely used in biomedical applications due to its hydrophilicity and biocompatibility. Exosomes are small vesicles secreted by nearly all cell types and play an important role in normal and pathological conditions. The purpose of this study was to eva...

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Autores principales: Ferrero-Andrés, Ana, Closa, Daniel, Roselló-Catafau, Joan, Folch-Puy, Emma
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7766665/
https://www.ncbi.nlm.nih.gov/pubmed/33353210
http://dx.doi.org/10.3390/polym12123044
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author Ferrero-Andrés, Ana
Closa, Daniel
Roselló-Catafau, Joan
Folch-Puy, Emma
author_facet Ferrero-Andrés, Ana
Closa, Daniel
Roselló-Catafau, Joan
Folch-Puy, Emma
author_sort Ferrero-Andrés, Ana
collection PubMed
description Polyethylene glycols (PEGs) are neutral polymers widely used in biomedical applications due to its hydrophilicity and biocompatibility. Exosomes are small vesicles secreted by nearly all cell types and play an important role in normal and pathological conditions. The purpose of this study was to evaluate the role of a 35-kDa molecular weight PEG (PEG35) on the modulation of exosome-mediated inflammation. Human macrophage-like cells THP-1, epithelial BICR-18, and CAPAN-2 cells were exposed to PEG35 prior to incubation with exosomes of different cellular origins. Exosome internalization was evaluated by confocal microscopy and flow cytometry. In another set of experiments, macrophages were treated with increasing concentrations of PEG35 prior to exposure with the appropriate stimuli: lipopolysaccharide, BICR-18-derived exosomes, or exosomes from acute pancreatitis-induced rats. Nuclear Factor Kappa B (NFκB) and Signal transducer and activator of transcription 3 (STAT3) activation and the expression levels of pro-inflammatory Interleukin 1β (IL1β) were determined. PEG35 administration significantly enhanced the internalization of exosomes in both macrophages and epithelial cells. Further, PEG35 ameliorated the inflammatory response induced by acute pancreatitis-derived exosomes by reducing the expression of IL1β and p65 nuclear translocation. Our results revealed that PEG35 promotes the cellular uptake of exosomes and modulates the pro-inflammatory effect of acute pancreatitis-derived vesicles through inhibition of NFκB, thus emphasizing the potential value of PEG35 as an anti-inflammatory agent for biomedical purposes.
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spelling pubmed-77666652020-12-28 Polyethylene Glycol 35 (PEG35) Modulates Exosomal Uptake and Function Ferrero-Andrés, Ana Closa, Daniel Roselló-Catafau, Joan Folch-Puy, Emma Polymers (Basel) Article Polyethylene glycols (PEGs) are neutral polymers widely used in biomedical applications due to its hydrophilicity and biocompatibility. Exosomes are small vesicles secreted by nearly all cell types and play an important role in normal and pathological conditions. The purpose of this study was to evaluate the role of a 35-kDa molecular weight PEG (PEG35) on the modulation of exosome-mediated inflammation. Human macrophage-like cells THP-1, epithelial BICR-18, and CAPAN-2 cells were exposed to PEG35 prior to incubation with exosomes of different cellular origins. Exosome internalization was evaluated by confocal microscopy and flow cytometry. In another set of experiments, macrophages were treated with increasing concentrations of PEG35 prior to exposure with the appropriate stimuli: lipopolysaccharide, BICR-18-derived exosomes, or exosomes from acute pancreatitis-induced rats. Nuclear Factor Kappa B (NFκB) and Signal transducer and activator of transcription 3 (STAT3) activation and the expression levels of pro-inflammatory Interleukin 1β (IL1β) were determined. PEG35 administration significantly enhanced the internalization of exosomes in both macrophages and epithelial cells. Further, PEG35 ameliorated the inflammatory response induced by acute pancreatitis-derived exosomes by reducing the expression of IL1β and p65 nuclear translocation. Our results revealed that PEG35 promotes the cellular uptake of exosomes and modulates the pro-inflammatory effect of acute pancreatitis-derived vesicles through inhibition of NFκB, thus emphasizing the potential value of PEG35 as an anti-inflammatory agent for biomedical purposes. MDPI 2020-12-18 /pmc/articles/PMC7766665/ /pubmed/33353210 http://dx.doi.org/10.3390/polym12123044 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ferrero-Andrés, Ana
Closa, Daniel
Roselló-Catafau, Joan
Folch-Puy, Emma
Polyethylene Glycol 35 (PEG35) Modulates Exosomal Uptake and Function
title Polyethylene Glycol 35 (PEG35) Modulates Exosomal Uptake and Function
title_full Polyethylene Glycol 35 (PEG35) Modulates Exosomal Uptake and Function
title_fullStr Polyethylene Glycol 35 (PEG35) Modulates Exosomal Uptake and Function
title_full_unstemmed Polyethylene Glycol 35 (PEG35) Modulates Exosomal Uptake and Function
title_short Polyethylene Glycol 35 (PEG35) Modulates Exosomal Uptake and Function
title_sort polyethylene glycol 35 (peg35) modulates exosomal uptake and function
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7766665/
https://www.ncbi.nlm.nih.gov/pubmed/33353210
http://dx.doi.org/10.3390/polym12123044
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