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

Autor: Riccardo Panella, Floriana Zanderigo, Francesca Morandini, Denise Federico, Elena Vicentini, Filippo Andreetta, Alessandro Toniolo, Sakari Kauppinen
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Frontiers in Pharmacology, Vol 14 (2023)
Druh dokumentu: article
ISSN: 1663-9812
DOI: 10.3389/fphar.2023.1125654
Popis: 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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