Cited by 1,008Neutrophil, Myeloperoxidase and Oxidative MechanismsRedox biology and oxidative stressNF-κB Signaling Pathways

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TNF and ROS Crosstalk in Inflammation

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Blaser, Heiko, Dostert, Catherine, Mak, Tak W., Brenner, Dirk·2016·Trends in Cell Biology

DOI 10.1016/j.tcb.2015.12.002

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Abstract

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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Wu, Y., Ma, R., & Jiang, H. (2026) · Frontiers in Musculoskeletal Disorders · doi:10.3389/fmscd.2026.1788598 · Cited by 1
“Oxidative stress leads to the accumulation of ROS, and excessive ROS induce cell apoptosis and increase the release of pro-inflammatory cytokines (69).”
Nuclear factor erythroid 2-related factor 2 gene expression in patients with heat stroke and its association with oxidative stress and inflammation: a prospective study
Lin, G., Guo, H., Yin, B., Xu, C., Chen, T., Zhao, Y., Wen, Q., Shao, Y., & Pan, Z. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1719289 · Cited by 1
Tunicamycin-induced ER stress promotes inflammation in SH-SY5Y cells through ROS-NF-κB-SIRT1 pathway
Jayan, S. G., NAIR, A. J., Boban, P. T., & Saja, K. (2026) · Molecular Biology Reports · doi:10.1007/s11033-026-11894-9 · Cited by 1
“TNF-α mediates immune response in various diseases [ 18].”
Revisiting intervertebral disc degeneration: lipid metabolism disorders as overlooked contributors to complex pathology
Chen, S., LIU, H., Wang, K., Wang, H. Y., Xu, A., Suo, M., Chen, X., & Li, Z. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1843872 · Cited by 1
“ROS increase TNF production, which contributes to ECM breakdown and the release of proin ﬂ ammatory factors in IVD cells by triggering the NF-k B and MAPK pathways, thereby establishing a positive feedback loop (156, 157).”
ROS-scavenging tetrahedral framework nucleic acids: reprogramming the pathological microenvironment for oral tissue regeneration
Xiong, J., Cui, W., Fu, X., Zhao, Z., Zhou, Y., Huang, B., Zhang, M., & Lin, Y. (2026) · Oral Science and Homeostatic Medicine · doi:10.26599/oshm.2026.9610064 · Cited by 1
Fluid–Matrix Interface Triggers a Heterogeneous Activation of Macrophages
Jo, Y., Kim, H. M., Lee, J., Lee, C., Hugonnet, H. J., Park, Y., Liu, X., Chang, Y., Kim, H., & Kim, P. (2020) · ACS Applied Bio Materials · doi:10.1021/acsabm.0c00345 · Cited by 1
Current Insights to Therapeutic Targets of ROS Induced Gastric Cancer Stem Cells
Nandan, A., Raghav, P. K., Srivastava, A., Tiwari, S. K., Shukla, A. K., & Sharma, V. (2021) · Handbook of Oxidative Stress in Cancer: Therapeutic Aspects · doi:10.1007/978-981-16-1247-3_255-1 · Cited by 1
The Interplay betweenSalmonella entericaSerovar Typhimurium and the Intestinal Mucosa during Oral Infection
Hausmann, A., & Hardt, W. (2020) · John Wiley & Sons, Inc. eBooks · doi:10.1128/9781683670261.ch3 · Cited by 1
ROS in Apoptosis of Cancer Cells
Bayır, A. G. (2021) · Springer eBooks · doi:10.1007/978-981-15-4501-6_41-1 · Cited by 1
The Effect of Alpha Lipoic Acid (ALA) Supplementation on the in Vitro Maturation Media of Goat Oocyte on Tumor Alpha Necrosis Factor (TNF-α) Expression and Malondialdehyde (MDA) Levels
Al-Anshori, A. A., Mustofa, I., Safitri, E., Mulyati, S., Rimayanti, R., Luqman, E. M., & Widjiati, W. (2023) · International Journal Of Scientific Advances · doi:10.51542/ijscia.v4i1.10 · Cited by 1
CARD9 deficiency improves the recovery of limb ischemia in mice with ambient fine particulate matter exposure
Zhu, Q., Liu, X., Wu, H., Yang, C., Wang, M., Chen, F., Cui, Y., Hao, H., Hill, M. A., & Liu, Z. (2023) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2023.1125717 · Cited by 1
“ROS in turn stimulates the expressions and releases of pro-inflammatory cytokines through activation of NF-κB signaling pathways (36, 37).”
Background
Anti-Inflammatory Activity of N′-(3-(1H-indol-3-yl)benzylidene)-2-cyanoacetohydrazide Derivative via sGC-NO/Cytokine Pathway
da Silva, P. R., Apolinário, N. D. M., da Silva, S. Â. S., Araruna, M. E. C., Costa, T. B., Silva, Y. M. S. D. M. E., da Silva, T. G., dos Santos, V. L., & de Moura, R. O. (2023) · Pharmaceuticals · doi:10.3390/ph16101415 · Cited by 3
“Thus, JR19 shows great promise in controlling inflammation”
Background
Necroptosis-related genes allow novel insights into predicting graft loss and diagnosing delayed graft function in renal transplantation
Wang, J., Lu, C., Wang, J., Wang, Y., Bi, H., Zheng, J., & Ding, X. (2023) · Genomics · doi:10.1016/j.ygeno.2023.110778 · Cited by 1
Mesenchymal stem cells as a promising therapy for alcohol use disorder
Gallardo, J., Berríos‐Cárcamo, P., & Ezquer, F. E. (2024) · International review of neurobiology · doi:10.1016/bs.irn.2024.07.002 · Cited by 1
Assessment on the Personal Exposure Risk Associated With Real‐Time Indoor PM2.5 in Different Microenvironments
Dai, S., He, Y., Zeng, N., & Wang, Z. (2024) · Indoor Air · doi:10.1155/2024/2236778 · Cited by 1
New Insights into the Toxic Effects of Different Sizes of Nanosilica Particles in Food on the Mouse Bladder: Involving Epithelial–Mesenchymal Transition
Yin, Y., Wang, J., Xu, T., Liu, M., Xu, S., & Xu, S. (2024) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.4c08353 · Cited by 1
Targeting NLRP3 inflammasome activation in styrene-induced ototoxicity: comparative efficacy of rosmarinic acid and anakinra in mitigating oxidative and inflammatory damage
Hassler, B., Hizam, V. M., Pisani, A., Sisto, R., Paciello, F., Grassi, C., & Fetoni, A. R. (2025) · International Journal of Audiology · doi:10.1080/14992027.2025.2566743 · Cited by 1
“…on one hand, the NF-j B dependent genes have been shown to impact the levels of ROS but, in turn, ROS production can also influence NF-j B activity (Yamamoto et al. 2009; Collins et al. 2012; Dan Dunn et al. 2015; Morgan and Liu 2011; Gloire, Legrand-Poels, and Piette 2006; Blaser et al. 2016).”
Cyclic Stretch Induces Inflammatory Cytokines via the Oxidative Stress and NF-ΚB Pathways Activation in Human Keratoconic Fibroblasts
Li, X., Wang, S., Song, J. Y., Qin, Y., Yang, J., He, R., & Chen, W. (2021) · Molecular & cellular biomechanics · doi:10.32604/mcb.2021.014071 · Cited by 1
“ROS are another key signaling molecule involved in the progression of inflammatory diseases [35,36].”
Background
Role of Toll-Like Receptors in Molecular and Cellular Mechanisms of Respiratory Diseases
Kanwar, I. L., Haider, T., Pandey, V., Gupta, P. N., & Soni, V. (2021) · Springer eBooks · doi:10.1007/978-981-33-6827-9_31 · Cited by 1
A Promising Approach to Improving COVID-19 Symptoms: Using Antioxidant Supplements
Shahbaz, S. K., Naderi, Y., Hedayati, S. K., & Aali, E. (2021) · The Journal of Qazvin University of Medical Sciences · doi:10.32598/jqums.25.2.1161.6 · Cited by 1
The Dietary Inflammatory Index
Aslani, Z., Nezamoleslami, S., & Qorbani, M. (2022) · Biomarkers in disease · doi:10.1007/978-3-030-81304-8_46-1 · Cited by 1
The Dietary Inflammatory Index
Aslani, Z., Nezamoleslami, S., & Qorbani, M. (2022) · Biomarkers in disease · doi:10.1007/978-3-031-07389-2_46 · Cited by 2
Vibrio vulnificus Hemolysin Induces TNF-α Independent ROS Production by Primary Murine MacrophagesPreprint
Lou, Y., Xie, D., Huang, X., Zheng, M., Zhang, T., & Xu, J. (2021) · Research Square · doi:10.21203/rs.3.rs-147505/v1 · Cited by 1
Is there an association between TNFR2 M196R polymorphism and acne vulgaris in Egyptian patients?
Ragab, M. A., El-Burdeni, M. M., Farid, C. I., & Elrashed, A. S. A. (2016) · Journal of the Egyptian Womenʼs Dermatologic Society · doi:10.1097/01.ewx.0000483163.04392.e8
Insulin resistance and Parkinson’s disease
Farooqui, A. A. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-819603-8.00007-9
Downregulation of Perilipin1 by IMD leads to LD reconfiguration and adaptation to bacterial infection in DrosophilaPreprint
Wang, L., Lin, J., Yu, J., Yang, K., Sun, L. M., Tang, H., & Pan, L. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.04.30.070292
“And one 313 hallmark is excessive lipolysis-induced lipotoxicity (Blaser et al., 2016; Grisouard et 314 al., 2012; Morgan and Liu, 2011; Zu et al., 2009), which is one causative factor for 315 reactive oxidative species (ROS)-related tissue damages(Ertunc and Hotamisligil, 2016; 316 Herms et al.,…”
Background
Μελέτη της επίδρασης του αναπνεόμενου όγκου σε μηχανικά αεριζόμενους ασθενείς χωρίς σημαντική πνευμονική βλάβη
Ζιάκα, Μ. (2021) · doi:10.12681/eadd/48842
ROS in Apoptosis of Cancer Cells
Bayır, A. G. (2021)
Identification and verification of the potential effect of therapeutic miRNA-mRNA pairs on ferroptosis in small cell lung cancer by bioinformatics analysisPreprint
Wu, Y. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.06.28.450166
“The abnormal alteration of this pathway affects immune and non-immune cell types, including macrophages, T cells, mast cells, granulocytes, natural killer (NK) cells, fibroblasts, neurons, keratinocytes, and smooth muscle cells as an immune response to pathogenic stimuli (Blaser et al. 2016).”
Background
Cytokine Storm and Immunomodulation in COVID-19: A Review
Tripathi, V., Arsh, A. M., Mishra, S., & Mishra, A. (2021) · Coronaviruses · doi:10.2174/2666796702666210913100327
Papel de la proteína quinasa C (PKC) en el crecimiento de células de leucemia linfoide aguda tipo B, en el soporte que les proporcionan las células stem mesenquimales y en su funcionalidad en un modelo in vitro de nicho leucémico
Avendaño, V., & Pilar, N.-D. (2021)
Dynein Light Chain LC8 Alleviates Nonalcoholic Steatohepatitis By Regulating Nuclear Factor κB Through Interference With IκBα PhosphorylationPreprint
Lee, G., Lee, H. I., Kim, N., Lee, J., Kwon, M., Kang, Y. H., Song, H. J., Yeo, C., & Jeong, W. (2021) · Research Square · doi:10.21203/rs.3.rs-906706/v1
Effector-mediated subversion of proteasome activator (PA)28αβ enhances host defense against Legionella pneumophila under inflammatory and oxidative stress conditionsPreprint
Ngwaga, T., Chauhan, D., Salberg, A. G., & Shames, S. R. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.12.27.473672
“Tnfr1-/- BMDMs were used to control for any LegC4-me332 diated differences in TNF secretion [20] and, consequently, intracellular ROS production [50].”
Method
Efeitos do Tempol, um mimético da superóxido dismutase, em fibras musculares distróficas de camundongos mdx
Hermes, T. D. A. (2018) · doi:10.47749/t/unicamp.2018.1096408
The search for monomer-interaction-based alternative TNF-α therapies
Farrugia, M., & Baron, B. (2022) · Elsevier eBooks · doi:10.1016/b978-0-12-824390-9.00013-x
Evidência e caracterização molecular da geração de espécies reativas em plaquetas na endotoxemia experimental
Naime, A. C. A. (2017) · doi:10.47749/t/unicamp.2017.986297
Pre-treatment controlling nutritional status (CONUT) score and carcinoembryonic antigen level provide tumour progression and prognostic information in gastric cancer: a retrospective studyPreprint
Chen, X., Yang, L., Huang, L., & Wu, P. (2022) · Research Square · doi:10.21203/rs.3.rs-116822/v2
ROS in Apoptosis of Cancer Cells
Bayır, A. G. (2022) · Springer eBooks · doi:10.1007/978-981-15-9411-3_41

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
ORCID: Mak, Tak W.
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)
DOI: 10.1016/j.tcb.2015.12.002
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
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
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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