Amin Mohedin Jabbar, Rezaiemanesh Alireza, Asadi Soheila, Haddadi Maryam, Abdul Ahmed Bahroz, Gorgin Karaji Ali, Salari Farhad
Student Research Committee, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran.
Department of Laboratory, Ministry of Health, Sulamania, KRG, Iraq.
Rep Biochem Mol Biol. 2024 Jan;12(4):566-574. doi: 10.61186/rbmb.12.4.566.
Chronic inflammation is associated with many inflammatory diseases. Specialized pro-resolving mediators (SPMs) are well known for their crucial role in promoting the resolution phase of inflammation and restoring tissue homeostasis. Resolvin D1 (RvD1) is an endogenous omega-3-derived lipid mediator with pro-resolving activity. This study aimed to evaluate the effect of Resolvin D1 (RvD1) on some inflammatory miRNAs (mir-155-5p, miR146a-5p and miR148-3p) and Krüppel-like factors 5 (KLF5) in an LPS-stimulated THP-1 preclinical model of inflammation.
PMA-differentiated THP-1 cells (macrophages) were pre-incubated with or without various concentrations of RvD1 (10, 50, or 100 nM) for 2 h prior to stimulation by 1 μg/ml LPS. Un-stimulated PMA-differentiated THP-1 cells were as the control group. Then, the expression levels of target genes were evaluated by real-time PCR.
Compared with untreated macrophages, stimulation with 1 µg/ml LPS increased mRNA expression levels of TNF-α, KLF5, miR-155-5p, miR-146-5p, and miR-148a-3p. When the cells were exposed to various concentrations (10, 50 and 100 nM) of RvD1 for 2 h prior to LPS stimulation, the TNF-α, KLF5, miR-155-5p, miR-146-5p, and miR-148a-3p mRNA expression levels were significantly downregulated in a dose-dependent manner, compared to the LPS group.
The results demonstrate that RvD1 can attenuate inflammatory response in LPS-stimulated macrophages. Our data also showed that RvD1 may exert anti-inflammatory effects by inhibiting miR-155-5p, miR-146a-5p, and miR-148-3p.
慢性炎症与多种炎症性疾病相关。特异性促消退介质（SPMs）因其在促进炎症消退阶段和恢复组织稳态中的关键作用而闻名。消退素D1（RvD1）是一种具有促消退活性的内源性ω-3衍生脂质介质。本研究旨在评估消退素D1（RvD1）对脂多糖（LPS）刺激的THP-1炎症临床前模型中一些炎性微小RNA（mir-155-5p、miR146a-5p和miR148-3p）及 Kruppel样因子5（KLF5）的影响。
用佛波酯（PMA）分化的THP-1细胞（巨噬细胞）在1 μg/ml LPS刺激前，预先用不同浓度（10、50或100 nM）的RvD1孵育2小时，未刺激的PMA分化的THP-1细胞作为对照组。然后，通过实时聚合酶链反应（PCR）评估靶基因的表达水平。
与未处理的巨噬细胞相比，1 μg/ml LPS刺激增加了肿瘤坏死因子-α（TNF-α）、KLF5、miR-155-5p、miR-146-5p和miR-148a-3p的mRNA表达水平。当细胞在LPS刺激前2小时暴露于不同浓度（10、50和100 nM）的RvD1时，与LPS组相比，TNF-α、KLF5、miR-155-5p、miR-146-5p和miR-148a-3p的mRNA表达水平呈剂量依赖性显著下调。
结果表明RvD1可减轻LPS刺激的巨噬细胞中的炎症反应。我们的数据还表明，RvD1可能通过抑制miR-155-5p、miR-146a-5p和miR-148-3p发挥抗炎作用。
