Is Nuclear Factor Erythroid 2-Related Factor 2 a Target for the Intervention of Cytokine Storms?

• Type of Material: Article
• Authors: Zihang Liu, China Medical University; Panpan Deng, China Medical University; Shengnan Liu, China Medical University; Yiying Bian, China Medical University; Yuanyuan Xu, China Medical University; Qiang Zhang, Emory University; Huihui Wang, China Medical University; Jingbo Pi, China Medical University
• Language: English
• Date: 2023-01-01
• Publisher: MDPI
• Publication Version: Final Published Version
• Copyright Statement: © 2023 by the authors.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.3390/antiox12010172
• Title of Journal or Parent Work: ANTIOXIDANTS
• Volume: 12
• Issue: 1
• Grant/Funding Information: This research was funded by the National Natural Science Foundation of China 81830099 (J.P.), 82020108027 (J.P.), 82073513 (H.W.) and 82022063 (Y.X.); National Key R&D Program of China of the Ministry of Science and Technology of the People’s Republic of China #2018YFC1311600 (J.P.); Natural Science Foundation of Liaoning Province 2022-MS-215 (H.W.); Shenyang Science and Technology Bureau of Support Program for Young Innovation Scholar RC210296 (H.W.); Innovation Team Support from China Medical University (CXTD2022004); High-level Talents Support Foundation from China Medical University 2400022052 (H.W.).
• Keywords: Food Science & Technology; SIGNALING PATHWAYS; ACUTE LUNG INJURY; ANTIOXIDANT RESPONSE; INFLUENZA-VIRUS INFECTION; HEME OXYGENASE-1; cytokine; NRF2; cytokine storm; oxidative stress; inflammation; OXIDATIVE STRESS; PPAR-GAMMA; Life Sciences & Biomedicine; Science & Technology; INDUCED INFLAMMATORY RESPONSE; KIDNEY INJURY; Biochemistry & Molecular Biology; NF-KAPPA-B; Pharmacology & Pharmacy; Chemistry, Medicinal
• Research Categories: Health Sciences, Toxicology; Health Sciences, Public Health

Abstract

The term “cytokine storm” describes an acute pathophysiologic state of the immune system characterized by a burst of cytokine release, systemic inflammatory response, and multiple organ failure, which are crucial determinants of many disease outcomes. In light of the complexity of cytokine storms, specific strategies are needed to prevent and alleviate their occurrence and deterioration. Nuclear factor erythroid 2-related factor 2 (NRF2) is a CNC-basic region-leucine zipper protein that serves as a master transcription factor in maintaining cellular redox homeostasis by orchestrating the expression of many antioxidant and phase II detoxification enzymes. Given that inflammatory response is intertwined with oxidative stress, it is reasonable to assume that NRF2 activation limits inflammation and thus cytokine storms. As NRF2 can mitigate inflammation at many levels, it has emerged as a potential target to prevent and treat cytokine storms. In this review, we summarized the cytokine storms caused by different etiologies and the rationale of interventions, focusing mainly on NRF2 as a potential therapeutic target.