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Assessment of immunostimulatory responses to the antimiR-22 oligonucleotide compound RES-010 in human peripheral blood mononuclear cells

microRNA-22 (miR-22) is a key regulator of lipid and energy homeostasis and represents a promising therapeutic target for NAFLD and obesity. We have previously identified a locked nucleic acid (LNA)-modified antisense oligonucleotide compound complementary to miR-22, designated as RES-010 that media...

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Autores principales: Panella, Riccardo, Zanderigo, Floriana, Morandini, Francesca, Federico, Denise, Vicentini, Elena, Andreetta, Filippo, Toniolo, Alessandro, Kauppinen, Sakari
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10076763/
https://www.ncbi.nlm.nih.gov/pubmed/37033600
http://dx.doi.org/10.3389/fphar.2023.1125654
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author Panella, Riccardo
Zanderigo, Floriana
Morandini, Francesca
Federico, Denise
Vicentini, Elena
Andreetta, Filippo
Toniolo, Alessandro
Kauppinen, Sakari
author_facet Panella, Riccardo
Zanderigo, Floriana
Morandini, Francesca
Federico, Denise
Vicentini, Elena
Andreetta, Filippo
Toniolo, Alessandro
Kauppinen, Sakari
author_sort Panella, Riccardo
collection PubMed
description microRNA-22 (miR-22) is a key regulator of lipid and energy homeostasis and represents a promising therapeutic target for NAFLD and obesity. We have previously identified a locked nucleic acid (LNA)-modified antisense oligonucleotide compound complementary to miR-22, designated as RES-010 that mediated robust inhibition of miR-22 function in cultured cells and in vivo. In this study we investigated the immune potential of RES-010 in human peripheral blood mononuclear cells (PBMCs). We treated fresh human peripheral blood mononuclear cells isolated from six healthy volunteers with different concentrations of the RES-010 compound and assessed its proinflammatory effects by quantifying IL-1β, IL-6, IFN-γ, TNF-α, IFN-α2a, IFN-β, IL-10, and IL-17A in the supernatants collected 24 h of treatment with RES-010. The T-cell activation markers, CD69, HLA-DR, and CD25 were evaluated by flow cytometry after 24 and 144 h of treatment, respectively, whereas cell viability was assessed after 24 h of treatment with RES-010. Our results show that RES-010 compound does not induce any significant immunostimulatory responses in human PBMCs in vitro compared to controls, implying that the proinflammatory potential of RES-010 is low.
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spelling pubmed-100767632023-04-07 Assessment of immunostimulatory responses to the antimiR-22 oligonucleotide compound RES-010 in human peripheral blood mononuclear cells Panella, Riccardo Zanderigo, Floriana Morandini, Francesca Federico, Denise Vicentini, Elena Andreetta, Filippo Toniolo, Alessandro Kauppinen, Sakari Front Pharmacol Pharmacology microRNA-22 (miR-22) is a key regulator of lipid and energy homeostasis and represents a promising therapeutic target for NAFLD and obesity. We have previously identified a locked nucleic acid (LNA)-modified antisense oligonucleotide compound complementary to miR-22, designated as RES-010 that mediated robust inhibition of miR-22 function in cultured cells and in vivo. In this study we investigated the immune potential of RES-010 in human peripheral blood mononuclear cells (PBMCs). We treated fresh human peripheral blood mononuclear cells isolated from six healthy volunteers with different concentrations of the RES-010 compound and assessed its proinflammatory effects by quantifying IL-1β, IL-6, IFN-γ, TNF-α, IFN-α2a, IFN-β, IL-10, and IL-17A in the supernatants collected 24 h of treatment with RES-010. The T-cell activation markers, CD69, HLA-DR, and CD25 were evaluated by flow cytometry after 24 and 144 h of treatment, respectively, whereas cell viability was assessed after 24 h of treatment with RES-010. Our results show that RES-010 compound does not induce any significant immunostimulatory responses in human PBMCs in vitro compared to controls, implying that the proinflammatory potential of RES-010 is low. Frontiers Media S.A. 2023-03-23 /pmc/articles/PMC10076763/ /pubmed/37033600 http://dx.doi.org/10.3389/fphar.2023.1125654 Text en Copyright © 2023 Panella, Zanderigo, Morandini, Federico, Vicentini, Andreetta, Toniolo and Kauppinen. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Panella, Riccardo
Zanderigo, Floriana
Morandini, Francesca
Federico, Denise
Vicentini, Elena
Andreetta, Filippo
Toniolo, Alessandro
Kauppinen, Sakari
Assessment of immunostimulatory responses to the antimiR-22 oligonucleotide compound RES-010 in human peripheral blood mononuclear cells
title Assessment of immunostimulatory responses to the antimiR-22 oligonucleotide compound RES-010 in human peripheral blood mononuclear cells
title_full Assessment of immunostimulatory responses to the antimiR-22 oligonucleotide compound RES-010 in human peripheral blood mononuclear cells
title_fullStr Assessment of immunostimulatory responses to the antimiR-22 oligonucleotide compound RES-010 in human peripheral blood mononuclear cells
title_full_unstemmed Assessment of immunostimulatory responses to the antimiR-22 oligonucleotide compound RES-010 in human peripheral blood mononuclear cells
title_short Assessment of immunostimulatory responses to the antimiR-22 oligonucleotide compound RES-010 in human peripheral blood mononuclear cells
title_sort assessment of immunostimulatory responses to the antimir-22 oligonucleotide compound res-010 in human peripheral blood mononuclear cells
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10076763/
https://www.ncbi.nlm.nih.gov/pubmed/37033600
http://dx.doi.org/10.3389/fphar.2023.1125654
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