The Time-Course of Antioxidant Irisin Activity: Role of the Nrf2/HO-1/HMGB1 Axis.
antioxidant
cytoprotection
inflammation
irisin
macrophages
Journal
Antioxidants (Basel, Switzerland)
ISSN: 2076-3921
Titre abrégé: Antioxidants (Basel)
Pays: Switzerland
ID NLM: 101668981
Informations de publication
Date de publication:
11 Jan 2021
11 Jan 2021
Historique:
received:
12
10
2020
revised:
12
11
2020
accepted:
08
01
2021
entrez:
14
1
2021
pubmed:
15
1
2021
medline:
15
1
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 33440644
pii: antiox10010088
doi: 10.3390/antiox10010088
pmc: PMC7827448
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : Uniwersytet Jagielloński w Krakowie
ID : N18/DBS/000007
Organisme : Uniwersytet Jagielloński Collegium Medicum
ID : N43/DBS/000047
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