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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1 retracted

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Background
Anticancer potential and through study of the cytotoxicity mechanism of ionic liquids that are based on the trifluoromethanesulfonate and bis(trifluoromethylsulfonyl)imide anions
Kuczak, M., Musiał, M., Malarz, K., Rurka, P., Zorębski, E., Musioł, R., Dzida, M., & Mrozek‐Wilczkiewicz, A. (2021) · Journal of Hazardous Materials · doi:10.1016/j.jhazmat.2021.128160 · Cited by 19
Glycyrrhetinic acid: A potential drug for the treatment of COVID-19 cytokine storm
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Danshensu Decreases UVB-Induced Corneal Inflammation in an Experimental Mouse Model via Oral Administration
Teng, M.-C., Wu, P. C., Lin, S.-P., Wu, C.-Y., Wang, P.-H., Chen, C.-T., & Chen, B.-Y. (2017) · Current Eye Research · doi:10.1080/02713683.2017.1379543 · Cited by 19
Redox modifications in synaptic components as biomarkers of cognitive status, in brain aging and disease
Muñoz, P., Ardiles, Á. O., Pérez-Espinosa, B., Núñez-Espinosa, C. A., Paula-Lima, A. C., González-Billault, C. E., & Espinosa‐Parrilla, Y. (2020) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2020.111250 · Cited by 21
“Additionally, inflammation and conditions where ROS and RNS levels reach high levels (Blaser et al., 2016), associated with aberrant Cxs and Panxs hemichannel activities occur in different brain cells, and neuronal death (Bargiotas et al.”
Background
A Deferoxamine-Loaded Microneedle Patch Enhances Healing of Radiation-Induced Skin Injury: Potential Involvement of Ferroptosis
Tian, K., Wu, P., Gao, S., Xu, C., Xu, W., Jia, Z., Wang, Y., Sheng, L., Zhou, X., Wu, S., et al. (2025) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.4c21589 · Cited by 18
The Effect of Endurance Training on Brain-Derived Neurotrophic Factor and Inflammatory Markers in Healthy People and Parkinson's Disease. A Narrative Review
Malczynska-Sims, P., Chalimoniuk, M., & Sułek, A. (2020) · Frontiers in Physiology · doi:10.3389/fphys.2020.578981 · Cited by 19
Development of a Machine Learning Model to Predict Non-Durable Response to Anti-TNF Therapy in Crohn’s Disease Using Transcriptome Imputed from Genotypes
Park, S. K., Kim, Y. B., Kim, S., Lee, C.-W., Choi, C. H., Kang, S., Kim, T. O., Bang, K. B., Chun, J., Cha, J. M., et al. (2022) · Journal of Personalized Medicine · doi:10.3390/jpm12060947 · Cited by 18
“The major role of TNF is to regulate the immune system through the activation of TNF receptors and downstream pathways involving molecules, such as nuclear factor kappa-B, mitogenactivated protein kinases, caspases, and ROS/reactive nitrogen species [30].”
Background
Uterine Fibroids Causing Preterm Birth: A New Pathophysiological Hypothesis on the Role of Fibroid Necrosis and Inflammation
Don, E. E., Landman, A. J. E. M. C., Vissers, G., Jordanova, E. S., Uiterweer, E. D. P., de Groot, C. J. M., de Boer, M. A., & Huirne, J. A. F. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23158064 · Cited by 19
“Moreover, intracellular ROS is involved in NF-κB signaling and the downstream production of TNF [71].”
Background
Connexin 43 (Cx43) regulates high-glucose-induced retinal endothelial cell angiogenesis and retinal neovascularization
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“It’s well-established that excessive ROS produced under various physiological and pathological conditions [such as inflammation (34) and ischemia (35)] may lead to the metabolic imbalance of oxidative stress-generated reactive intermediates and multiple disorders, including DR (36, 37).”
Background
Curcumin treatment attenuates cisplatin-induced gastric mucosal inflammation and apoptosis through the NF- κ B and MAPKs signaling pathway
Gao, J., Liu, Y., Chen, J., Tong, C., Wang, Q., & Piao, Y. (2022) · Human & Experimental Toxicology · doi:10.1177/09603271221128738 · Cited by 18
“Some stress signals, such as reactive oxygen species (ROS) and inflammatory cytokines, were reported to cause the degradation of I κ B subunit, and then released NF-κB as transcription factors of proinflammatory adhesion molecules and cytokines.(15) Mitogen-activated protein kinase (MAPKs) pathway, including p38MAPK,…”
Background
Oxidized Proteins Differentially Affect Maturation and Activation of Human Monocyte-Derived Cells
Clemen, R., Arlt, K., Miebach, L., von Woedtke, T., & Bekeschus, S. (2022) · Cells · doi:10.3390/cells11223659 · Cited by 18
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Alterations in intestinal microbiota and metabolites in individuals with Down syndrome and their correlation with inflammation and behavior disorders in mice
Cai, S., Lin, J., Li, Z., Liu, S., Feng, Z., Zhang, Y., Zhang, Y., Huang, J., & Chen, Q. (2023) · Frontiers in Microbiology · doi:10.3389/fmicb.2023.1016872 · Cited by 19
Garcinone C attenuates RANKL-induced osteoclast differentiation and oxidative stress by activating Nrf2/HO-1 and inhibiting the NF-kB signaling pathway
Ji, H., Pan, Q., Cao, R., Li, Y., Yang, Y., Chen, S., Gu, Y., Qian, D., Guo, Y., Wang, L., et al. (2024) · Heliyon · doi:10.1016/j.heliyon.2024.e25601 · Cited by 18
Ultrasonic-assisted extraction of polysaccharide from Paeoniae Radix alba: Extraction optimization, structural characterization and antioxidant mechanism in vitro
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Effect of melatonin supplementation on cardiometabolic risk factors, oxidative stress and hormonal profile in PCOS patients: a systematic review and meta-analysis of randomized clinical trials
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“TNF-α can increase the expression of NOX by activating NF-κB signaling, thereby inducing the generation of ROS [38, 39].”
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HEMA modulates the transcription of genes related to oxidative defense, inflammatory response and organization of the ECM in human oral cells
Perduns, R., Volk, J., Schertl, P., Leyhausen, G., & Geurtsen, W. (2019) · Dental Materials · doi:10.1016/j.dental.2019.01.011 · Cited by 18
Cytotoxicity analysis of ambient fine particle in BEAS-2B cells on an air-liquid interface (ALI) microfluidics system
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Anti-Inflammatory Potential of Cultured Ginseng Roots Extract in Lipopolysaccharide-Stimulated Mouse Macrophages and Adipocytes
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“Host defensive systems could be disrupted by the aberrant production of inflammatory signaling, pro-inflammatory gene expression, ROS, and cytokine production in macrophages [12,31].”
Background
HEMA-induced oxidative stress inhibits NF-κB nuclear translocation and TNF release from LTA- and LPS-stimulated immunocompetent cells
Schweikl, H., Birke, M., Gallorini, M., Petzel, C., Bolay, C., Waha, C., Hiller, K., & Buchalla, W. (2020) · Dental Materials · doi:10.1016/j.dental.2020.10.029 · Cited by 18
Circulating Endothelial Progenitor Cells Are Preserved in Female Mice Exposed to Ambient Fine Particulate Matter Independent of Estrogen
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Background
Dual-Specificity Phosphatase 1 (DUSP1) Has a Central Role in Redox Homeostasis and Inflammation in the Mouse Cochlea
Bermúdez‐Muñoz, J. M., Celaya, A. M., García-Mato, Á., Muñoz‐Espín, D., la Rosa, L. R., Serrano, M., & Varela‐Nieto, I. (2021) · Antioxidants · doi:10.3390/antiox10091351 · Cited by 18
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Effect of hypoxia/reoxygenation on the biological effect of IGF system and the inflammatory mediators in cultured synoviocytes
Zhou, S., Wen, H., Cai, W., Zhang, Y., & Li, H. (2019) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2018.11.099 · Cited by 16
Baicalin n-butyl ester alleviates inflammatory bowel disease and inhibits pyroptosis through the ROS/ERK/P-ERK/NLRP3 pathway in vivo and in vitro
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A multi-physically cross-linked roxadustat-loaded hydrogel for promoting diabetic wound healing via antibacterial, antioxidant and angiogenesis acceleration functions
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Protective effect of Rosuvastatin on Azithromycin induced cardiotoxicity in a rat model
Mansour, B. S. A., Salem, N. A., Kader, G. A., Abdel-Alrahman, G., & Mahmoud, O. M. (2021) · Life Sciences · doi:10.1016/j.lfs.2021.119099 · Cited by 17
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Enterocyte superoxide dismutase 2 deletion drives obesity
García‐Irigoyen, O., Bovenga, F., Piglionica, M., Piccinin, E., Cariello, M., Arconzo, M., Peres, C., Corsetto, P. A., Rizzo, A. M., Ballanti, M., et al. (2021) · iScience · doi:10.1016/j.isci.2021.103707 · Cited by 17
The Role of Tea Tree Oil in Alleviating Palmitic Acid-Induced Lipid Accumulation in Bovine Hepatocytes
Yang, T., Ma, X., Jiang, M., Cheng, Z., Datsomor, O., Zhao, G., & Zhan, K. (2022) · Frontiers in Veterinary Science · doi:10.3389/fvets.2021.814840 · Cited by 17
RIP3-Dependent Accumulation of Mitochondrial Superoxide Anions in TNF-α-Induced Necroptosis
Lee, J., Lee, S., Min, S., & Kang, S. W. (2022) · Molecules and Cells · doi:10.14348/molcells.2021.0260 · Cited by 17
“Two major ROS sources related to the TNF-α-induced cell death are NADPH oxidase (NOX) and mitochondria (Blaser et al., 2016; Morgan and Liu, 2010).”
Background
Blue Light Induces RPE Cell Necroptosis, Which Can Be Inhibited by Minocycline
Song, W., Zhu, R., Gao, W., Chen, X., & Yang, L. (2022) · Frontiers in Medicine · doi:10.3389/fmed.2022.831463 · Cited by 17
“High levels of ROS result in oxidative stress, and low levels of ROS regulate signaling pathways (24, 25).”
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Tectoridin alleviates lipopolysaccharide-induced inflammation via inhibiting TLR4-NF-κB/NLRP3 signaling in vivo and in vitro
Niu, X., Song, H., Xiao, X., Yu, J., Yu, J., Yang, Y., Huang, Q., Zang, L., Han, T., Zhang, D., et al. (2022) · Immunopharmacology and Immunotoxicology · doi:10.1080/08923973.2022.2073890 · Cited by 17
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Toxic effects of zinc oxide nanoparticles as a food additive in goat mammary epithelial cells
Wang, Z., He, Y., Liu, S., Xu, X., Song, Y., Zhang, L., & An, X. (2023) · Food Research International · doi:10.1016/j.foodres.2023.112682 · Cited by 17
Identification and characterization of the ferroptosis-related ceRNA network in irreversible pulpitis
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“Apoptosis was first discovered as a form of programmed cell death associated with inflammation pathways such as TNF and TRAIL receptors, together with downstream ROS/RNS signaling (12, 13).”
Increased blood reactive oxygen species and hepcidin in obstructive sleep apnea precludes expected erythrocytosis
Song, J., Sundar, K. M., Horváthová, M., Gangaraju, R., Indrák, K., Christensen, R. D., Genzor, S., Lundby, C., Divoký, V., Ganz, T., et al. (2023) · American Journal of Hematology · doi:10.1002/ajh.26992 · Cited by 17
“associated with thrombotic, atherosclerotic, and inflammatory changes.(40) Secondly, the absence of erythrocytosis in OSA is partly due to the suppression of erythropoiesis by increased inflammation and hepcidin.”
Background
Curcumin targets YAP1 to enhance mitochondrial function and autophagy, protecting against UVB-induced photodamage
Chen, Q., Lin, W., Tang, Y., He, F., Liang, B., Chen, J., Li, H., & Zhu, H. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1566287 · Cited by 17
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Retracted
Why do anti-inflammatory signals of bone marrow-derived stromal cells improve neurodegenerative conditions where anti-inflammatory drugs fail?
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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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