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TNF and ROS Crosstalk in Inflammation
Open accessAbstract
Tumor necrosis factor (TNF) is tremendously important for mammalian immunity and cellular homeostasis. The role of TNF as a master regulator in balancing cell survival, apoptosis and necroptosis has been extensively studied in various cell types and tissues. Although these findings have revealed much about the direct impact of TNF on the regulation of NF-κB and JNK, there is now rising interest in understanding the emerging function of TNF as a regulator of the generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS). In this review we summarize work aimed at defining the role of TNF in the control of ROS/RNS signaling that influences innate immune cells under both physiological and inflammatory conditions.
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“Besides, chronic inflammatory environment is also beneficial for the formation of free radicals such as reactive oxygen species (ROS), exacerbating β cells damage and yielding a positive feedback circle with the secretion of more detrimental cytokines to trigger further damage to β cells (80).”
From Diabetes and Sarcopenic Obesity: Pathogenesis, Diagnosis, and Treatments (2020) · cites this paper as [80]
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“…CNS, cholinergic neurotransmission occurs within important brain areas concerning cognitive and motor functions, like the cortex, striatum, and hippocampus, dysfunctions on ACh signaling became an important therapeutic target in neurodegeneration and dementia (Mesulam 1998; Bohnen and Albin 2011).”
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“28, 29 It also depletes intracellular glutathione, which contributes to its pro-oxidant actions.”
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“56 Notably, ROS are important inducers of the TNF signaling pathway, 57 and Fe-HCOF-PEG 2000 probably has no influence on immune responses without NIR stimulation.”
BackgroundTNF-α inhibits Epstein Barr virus reactivation through the GPX4 mediated glutathione pathway
Zhang, Y., Wu, Y., Ding, B., Li, Q., Chen, X., Liu, H., Xu, M., Lan, Y., & Li, Y. (2025) · Scientific Reports · doi:10.1038/s41598-025-98679-5 · Cited by 8
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Functional Variants Associated With CMPK2 and in ASB16 Influence Bovine Digital Dermatitis
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“In addition to the role of mitochondrial CMPK2 in nucleotide synthesis, KEGG pathway analysis shows that the activity of CMPK2 also contributes to production of amino acids and to DNA repair mechanisms, maintaining the vitality of activated proinflammatory macrophages (Blaser et al., 2016; Kanehisa et al., 2018).”
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“A vicious cycle exists in which ROS activate JNK and mitochondrial outer membrane protein-dependent ROS production, resulting in increased ROS production and sustained JNK activation (Blaser et al., 2016; Chambers and LoGrasso, 2011; Win et al., 2014).”
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“It is also known that signaling pathways activating NF-kB and consequent TNF-α expression can be modulated by ROS, proposing a mutual positive influence between ROS generation and TNF-α upregulation [58].”
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Myeloid cell dynamics in bleomycin-induced pulmonary injury in mice; effects of anti-TNFα antibody
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Cytokines Induced by Edwardsiella tarda: Profile and Role in Antibacterial Immunity
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“TNF–α is a factor with potent pro-inflammatory activity [15].”
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The janus face of oxidative stress in health and disease: The cause or the cure?
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“In addition to the mitochondrial production of superoxide anion, cyclooxygenase and lipoxygenase produce this ROS as a by-product [12,13], and NADPH oxidase produces it as a primary product [7,8,15].”
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“, thereby causing an inflammatory response [13].”
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“Some studies have suggested that the activation of JNK signaling pathway is involved in CIN cells, and the mechanism may be related to excessive ROS production.(23) We performed a series of experiments in ESCC cells to verify this mechanism.”
MethodCannabidiol Protects Striatal Neurons by Attenuating Endoplasmic Reticulum Stress
Patel, V., Abu-Hijleh, F. A., Rigg, N., & Mishra, R. K. (2022) · Cannabis and Cannabinoid Research · doi:10.1089/can.2022.0090 · Cited by 7
“21 25–27 CBD has displayed antioxidant properties against toxins used to model neurodegenerative disorders.”
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Metadata
- Authors
- Blaser, H., Dostert, C., Mak, T. W., & Brenner, D.
- Affiliations
- University Health Network (CA)
- Luxembourg Institute of Health (LU)
- University of Southern Denmark (DK)
- Corresponding author
- Brenner, Dirk
- Venue
- Trends in Cell Biology
- Publisher
- Elsevier BV
- Published
- 2016-04
- Volume
- 26
- Issue
- 4
- Pages
- 249-261
- ISSN
- 0962-8924 (ISSN-L)
- OpenAlex
- W2236270374
- Cited by
- 1,008
- References
- 131
- Citations by year
- 2026: 75 · 2025: 89 · 2024: 114 · 2023: 134 · 2022: 147 · 2021: 143 · 2020: 110 · 2019: 73 · 2018: 53 · 2017: 51 · 2016: 19
- FWCI
- 6.29
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Trends in Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- Open Repository and Bibliography (University of Luxembourg) (submittedVersion, other-oa)
- University of Southern Denmark Research Portal (University of Southern Denmark) (submittedVersion)
- Funders
- Fonds National de la Recherche Luxembourg (C15/BM/10355103)
- Canadian Institutes of Health Research (S2B141816)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Keywords
- TNF-α, reactive oxygen species, reactive nitrogen species, inflammation, innate immunity, NF-κB signaling, JNK signaling, apoptosis, necroptosis, cell survival, innate immune cells
- MeSH terms
- Animals, Cell Survival, Gene Expression Regulation, Homeostasis, Humans, Immunity, Innate, Inflammation, Lymphocytes, Necrosis, Tumor Necrosis Factor-alpha, Signal Transduction, NF-kappa B, Apoptosis, Reactive Oxygen Species, Reactive Nitrogen Species, MAP Kinase Kinase 4
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