The Time-Course of Antioxidant Irisin Activity: Role of the Nrf2/HO-1/HMGB1 Axis

Mazur-Bialy, Agnieszka Irena and Pocheć, Ewa (2021) The Time-Course of Antioxidant Irisin Activity: Role of the Nrf2/HO-1/HMGB1 Axis. Antioxidants, 10 (1). p. 88. ISSN 2076-3921

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Abstract

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.

Item Type: Article
Subjects: Scholar Eprints > Agricultural and Food Science
Depositing User: Managing Editor
Date Deposited: 01 Jul 2023 06:51
Last Modified: 05 Jun 2024 10:36
URI: http://repository.stmscientificarchives.com/id/eprint/2217

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