Panella Riccardo, Zanderigo Floriana, Morandini Francesca, Federico Denise, Vicentini Elena, Andreetta Filippo, Toniolo Alessandro, Kauppinen Sakari
Center for RNA Medicine, Department of Clinical Medicine, Aalborg University, Copenhagen, Denmark.
Resalis Therapeutics S.r.l., Torino, Italy.
Front Pharmacol. 2023 Mar 23;14:1125654. doi: 10.3389/fphar.2023.1125654. eCollection 2023.
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 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 compared to controls, implying that the proinflammatory potential of RES-010 is low.
微小RNA-22（miR-22）是脂质和能量稳态的关键调节因子，是治疗非酒精性脂肪性肝病（NAFLD）和肥胖症的一个有前景的治疗靶点。我们之前鉴定出一种与miR-22互补的锁核酸（LNA）修饰的反义寡核苷酸化合物，命名为RES-010，它在培养细胞中介导了对miR-22功能的强效抑制。在本研究中，我们调查了RES-010在人外周血单核细胞（PBMCs）中的免疫潜力。我们用不同浓度的RES-010化合物处理从6名健康志愿者分离的新鲜人外周血单核细胞，并通过定量RES-010处理24小时后收集的上清液中的白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）、干扰素-γ（IFN-γ）、肿瘤坏死因子-α（TNF-α）、干扰素-α2a（IFN-α2a）、干扰素-β（IFN-β）、白细胞介素-10（IL-10）和白细胞介素-17A（IL-17A）来评估其促炎作用。分别在处理24小时和144小时后通过流式细胞术评估T细胞活化标志物CD69、人类白细胞抗原-DR（HLA-DR）和CD25，而在用RES-010处理24小时后评估细胞活力。我们的结果表明，与对照组相比，RES-010化合物在人PBMCs中不会诱导任何显著的免疫刺激反应，这意味着RES-010的促炎潜力较低。
