Cited by 1,200Genomics, phytochemicals, and oxidative stressNF-κB Signaling PathwaysRedox biology and oxidative stress

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Dissecting molecular cross-talk between Nrf2 and NF-κB response pathways

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Wardyn, Joanna D., Ponsford, Amy H., Sanderson, Christopher M.·2015·Biochemical Society Transactions

DOI 10.1042/bst20150014PMC PMC4613495

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Abstract

In most tissues, cells are exposed to frequent changes in levels of oxidative stress and inflammation. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and nuclear factor-κB (NF-κB) are the two key transcription factors that regulate cellular responses to oxidative stress and inflammation respectively. Pharmacological and genetic studies suggest that there is functional cross-talk between these two important pathways. The absence of Nrf2 can exacerbate NF-κB activity leading to increased cytokine production, whereas NF-κB can modulate Nrf2 transcription and activity, having both positive and negative effects on the target gene expression. This review focuses on the potentially complex molecular mechanisms that link the Nrf2 and NF-κB pathways and the importance of designing more effective therapeutic strategies to prevent or treat a broad range of neurological disorders.

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“33,34 In light of the intricate connections between in ﬂ ammation, oxidative stress and IR, and considering the well-documented antioxidative and anti-in ﬂ ammatory capacity of OFIF, we have here evaluated if OFIF supplementation could counteract the obesity-induced, and oxy-in ﬂ ammation-related,…”
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“…expression that indirectly promotes NRF2 activity and therefore tumor progression and resistance to therapies; finally, IKK β activates NF-κ B pathway by phosphorylating and inducing I κ B-α (an inhibitor of NF-κ B) degradation, and also inhibits NRF2 through direct and indirect mechanisms [ 109].”
Holstein cow milk–derived Lactobacillus plantarum L19 alleviates heat stress–induced liver injury in mice by modulating gut microbiota
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“In the absence of Nrf2, pronounced NF-κ B activity leads to increased cytokine production [136].”
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“In addition, Nrf2 prevents proteasomal degradation of Ik-βα, inhibits nuclear translocation of NF-κB, and enhances HO-1 expression, consequently increasing transcription of phase II enzymes that block Ik-βα degradation and the NF-κB inhibitor [63, 86].”
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A mixture of extracts from natural ingredients reduces the neurotoxic polarization of microglia via modulating NF‐κB / NF‐E2 ‐related factor 2 activation
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“…by the mixture may contribute to shifting the microglia to neuroprotective phenotypes in AL-exposed microglia because the absence of Nrf2 exaggerates NF-κ B activity by enhancing I κ B α degradation (Rojo et al., 2010), while NF-κ B subunit p65 downregulates Nrf2 activity (Wardyn et al., 2015).”
Background
KEAP1-Mutant Lung Cancers Weaken Anti-Tumor Immunity and Promote an M2-like Macrophage Phenotype
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“…immune cell-specific NRF2 activation includes blocking proinflammatory cytokine transcription in M1-like macrophages [14,15]; promoting an M2-like macrophage secretory phenotype [16]; decreasing inflammatory cytokine transcription in lymphocytes [17]; and downregulating the NF-kB pathway [18,19].”
Background
The Triterpenoid CDDO-Methyl Ester Reduces Tumor Burden, Reprograms the Immune Microenvironment, and Protects from Chemotherapy-Induced Toxicity in a Preclinical Mouse Model of Established Lung Cancer
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“Additionally, an inverse relationship between the Nrf2 and NF-κ B pathways mediates many pro-inflammatory pathways under the transcriptional control of NF-κ B [77].”
Background
Intestinal Region-Dependent Impact of NFκB-Nrf Crosstalk in Myenteric Neurons and Adjacent Muscle Cells in Type 1 Diabetic Rats
Barta, B. P., Onhausz, B., Egyed-Kolumbán, A., Doghmi, A. A., Balázs, J., Szalai, Z., Ferencz, Á., Hermesz, E., Bagyánszki, M., & Bódi, N. (2024) · Biomedicines · doi:10.3390/biomedicines12102347 · Cited by 5
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“B activity, resulting in increased inflammatory cytokine release in kidney injury in rodents [46].”
Background
Characterization of a Clinically and Biologically Defined Subgroup of Patients with Autism Spectrum Disorder and Identification of a Tailored Combination Treatment
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“A crosstalk between NF-κ B and NRF2 has already been established [38].”
Background
Hydroethanolic Extract of Polygonum aviculare L. Mediates the Anti-Inflammatory Activity in RAW 264.7 Murine Macrophages Through Induction of Heme Oxygenase-1 and Inhibition of Inducible Nitric Oxide Synthase
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LMTK2 regulates inflammation in lipopolysaccharide‑stimulated BV2 cells
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“There is a crosstalk between the Nrf and NF‐κB pathways (24).”
Background
Lipid Peroxidation as a Link between Unhealthy Diets and the Metabolic Syndrome
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“Nrf2 activation in peritoneal macrophages decreases the production of COX-2 (cyclooxygenase 2), TNFα, iNOS (inducible nitric oxide synthase), and IL-1β in response to lipopolysaccharides [94,95].”
Background
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“Nuclear Factor Erythroid Related Factor 2 (Nrf2) and Nuclear Factor-Kappa B (NFkB) are key regulators of the body’s response to oxidative stress and inflammatory response 72 .”
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Preventive effects of quercetin against inflammation and apoptosis in cyclophosphamide-induced testicular damage.
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“According to studies, it has been reported that Nrf2 activates the antioxidant defense system by antagonizing NFkB activity (50, 51).”
Background
A Novel Analog of the Natural Product Fraxinellone Protects against Endogenous and Exogenous Neurotoxicants
Bartman, A. E., Raeisi, M., Peiris, C. D., Jacobsen, I. E., Martin, D. B. C., & Doorn, J. A. (2024) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.4c00090 · Cited by 4
Heat-not-burn technology affects plasma testosterone levels and markers of inflammation, oxidative stress in the testes of rats
Granata, S., Morosini, C., Valerii, M. C., Fagiolino, I., Sangiorgi, S., Ghini, S., Spisni, E., Vivarelli, F., Fairclough, L. C., Paolini, M., et al. (2025) · Frontiers in Toxicology · doi:10.3389/ftox.2024.1515850 · Cited by 4
Molecular Mechanisms of the Cardiotoxic Action of Anthracycline Antibiotics and Statin-Induced Cytoprotective Reactions of Cardiomyocytes
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Nrf2 regulates the expression of NOX1 in TNF-α-induced A549 cells
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A genome-wide CRISPR screen in human prostate cancer cells reveals drivers of macrophage-mediated cell killing and positions AR as a tumor-intrinsic immunomodulator
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Effect and mechanism of Qing Gan Zi Shen decoction on heart damage induced by obesity and hypertension
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Mild Oxidative Stress Induced by Sodium Arsenite Reduces Lipocalin-2 Expression Levels in Cortical Glial Cells
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“…2 (Nrf2)–Kelch-like ECH-associated protein 1 (Keap1) pathway, the major antioxidant response pathway, has been suggested to suppress NF-κ B signaling based on their molecular crosstalk, these two pathways may not interact or their interaction might be complex in astroglial-enriched cells [23].”
BackgroundMethod
Understanding One Half of the Sex Difference Equation
Visanji, M., Venegas-Pino, D. E., & Werstuck, G. H. (2023) · American Journal Of Pathology · doi:10.1016/j.ajpath.2023.11.009 · Cited by 4

Authors: Wardyn, J. D., Ponsford, A. H., & Sanderson, C. M.
Affiliations: University of Liverpool (GB)
Corresponding author: Sanderson, Christopher M.
ORCID: Ponsford, Amy H.
Sanderson, Christopher M.
Venue: Biochemical Society Transactions
Publisher: Portland Press Ltd.
Published: 2015-08-01
Volume: 43
Issue: 4
Pages: 621-626
ISSN: 0300-5127 (ISSN-L)
1470-8752
DOI: 10.1042/bst20150014
PMC: PMC4613495
OpenAlex: W2133584350
Cited by: 1,200
References: 53
Citations by year: 2026: 139 · 2025: 131 · 2024: 117 · 2023: 145 · 2022: 165 · 2021: 154 · 2020: 124 · 2019: 95 · 2018: 68 · 2017: 44 · 2016: 15 · 2015: 1
FWCI: 4.09
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Biochemical Society Transactions (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: Wellcome Trust (096564/Z/11/Z)
Directorate for Biological Sciences
Biotechnology and Biological Sciences Research Council (1222890, BB/J014516/1)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics, phytochemicals, and oxidative stress
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
Keywords: Nrf2, NF-κB, oxidative stress, inflammation, cytokine production, neurological disorders, treatment options
MeSH terms: Animals, Gene Expression Regulation, Humans, Nervous System Diseases, Signal Transduction, Cytokines, NF-kappa B, Oxidative Stress, NF-E2-Related Factor 2

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Dissecting molecular cross-talk between Nrf2 and NF-κB response pathways

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