Mazur-Bialy Agnieszka Irena, Pocheć Ewa
Department of Biomechanics and Kinesiology, Institute of Physiotherapy, Faculty of Health Science, Jagiellonian University Medical College, Grzegorzecka 20, 31-531 Krakow, Poland.
Department of Glycoconjugate Biochemistry, Institute of Zoology and Biomedical Research, Faculty of Biology, Jagiellonian University, Gronostajowa 9, 30-387 Krakow, Poland.
Antioxidants (Basel). 2021 Jan 11;10(1):88. doi: 10.3390/antiox10010088.
The production of free radicals is one of the basic mechanisms giving rise to the antimicrobial activity of macrophages; however, excessive accumulation of reactive oxygen species (ROS) can lead to cell damage, cell death, and release of the highly proinflammatory alarmin high-mobility group box 1 (HMGB1). This study aimed to evaluate the kinetics of antioxidant properties of the adipomyokine irisin administered shortly before or after macrophage activation to assess its effect on the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1)/HMGB1 pathway. The studies were performed on RAW 264.7 mouse macrophages treated with irisin (0, 25, and 50 nM) 2 h before or after lipopolysaccharide (LPS) stimulation. The effectiveness of respiratory burst and the expression of key factors of the antioxidant pathway, such as HO-1, Nrf2, superoxide dismutase 1 (SOD-1), SOD-2, glutathione peroxidase (GPx), catalase-9 (Cat-9), and HMGB1, were assessed. Irisin (50 nM) effectively reduced the free-radical production by macrophages. Furthermore, in both models, irisin altered the kinetics of expression of key factors of the downstream Nrf2/HO-1/HMGB1 pathway, leading to the increased production of Nrf2 and HO-1 and significantly reduced expression and release of HMGB1. In conclusion, irisin is a modulator of the Nrf2/HO-1/HMGB1 pathway and shows antioxidative and anti-inflammatory effects when administered both before and shortly after the activation of inflammatory mechanisms in mouse macrophages.
自由基的产生是巨噬细胞产生抗菌活性的基本机制之一；然而，活性氧（ROS）的过度积累会导致细胞损伤、细胞死亡，并释放具有高度促炎作用的警报素高迁移率族蛋白B1（HMGB1）。本研究旨在评估在巨噬细胞激活之前或之后不久给予脂肪肌动蛋白鸢尾素的抗氧化特性动力学，以评估其对核因子红细胞2相关因子2（Nrf2）/血红素加氧酶-1（HO-1）/HMGB1通路的影响。研究在脂多糖（LPS）刺激前或后2小时用鸢尾素（0、25和50 nM）处理的RAW 264.7小鼠巨噬细胞上进行。评估了呼吸爆发的有效性以及抗氧化途径关键因子的表达，如HO-1、Nrf2、超氧化物歧化酶1（SOD-1）、SOD-2、谷胱甘肽过氧化物酶（GPx）、过氧化氢酶-9（Cat-9）和HMGB1。鸢尾素（50 nM）有效降低了巨噬细胞产生的自由基。此外，在两种模型中，鸢尾素改变了下游Nrf2/HO-1/HMGB1通路关键因子的表达动力学，导致Nrf2和HO-1的产生增加，HMGB1的表达和释放显著降低。总之，鸢尾素是Nrf2/HO-1/HMGB1通路的调节剂，在小鼠巨噬细胞炎症机制激活之前和之后不久给予时均显示出抗氧化和抗炎作用。
