ArticleThe Journal of biological chemistry2012
5,6-Dimethylxanthenone-4-acetic acid (DMXAA) activates stimulator of interferon gene (STING)-dependent innate immune pathways and is regulated by mitochondrial membrane potential.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 130 papers.
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Who cites it
130 citing papers in PubMed, 210 citations in OpenAlex.
- A versatile cGAMP reporter reveals principles of cGAS activation by DNA damage and chromosome instability.Nature cell biology · 2026Article
- Optineurin calibrates STING-mediated type I interferon response.The FEBS journal · 2026Article
- Recent progress in cGAS-STING agonist design and mechanisms of cancer immune modulation.RSC chemical biology · 2026Review
- Mitochondrial reactive oxygen species regulate HIF-1α stabilization and methylglyoxal accumulation in classically activated mouse macrophages.Immunometabolism (Cobham, Surrey) · 2026Review
- DMXAA accelerates orthodontic tooth movement via macrophage-mediated Rab13-enriched extracellular vesicle release and chemokine secretion.Progress in orthodontics · 2026Article
- STING agonists as antiviral agents.FEBS letters · 2026Review
- Targeted Lipid Metabolism Screening Uncovers Regulatory Effects on the STING Immune Response in Mevalonate, Eicosanoid and Fatty Acid Pathways.bioRxiv : the preprint server for biology · 2026Article
- Targeted lipid metabolism screening uncovers regulatory effects on the STING immune response in mevalonate, eicosanoid and fatty acid pathways.Frontiers in immunology · 2026Article
- Advances and Strategies in Enhancing mRNA Cancer Vaccines.Advanced materials (Deerfield Beach, Fla.) · 2025Review
- Emerging cGAS-STING Agonist-Based Nanotherapeutics: Mechanistic Insights and Applications in Cancer Combination Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- STING COPII ER Export Trafficking and Signaling Primed by Phosphorylation Switches.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Metal-organic frameworks activate the cGAS-STING pathway for cancer immunotherapy.Journal of nanobiotechnology · 2025Review
- Demystifying the cGAS-STING pathway: precision regulation in the tumor immune microenvironment.Molecular cancer · 2025Review
- Progress Update on STING Agonists as Vaccine Adjuvants.Vaccines · 2025Review
- Intracellular methylglyoxal accumulation in classically activated mouse macrophages is mediated by HIF-1α.Journal of leukocyte biology · 2025Article
- Universal STING Pathway-Activating Complexes Counteract Viral Immune Evasion and Boost Antiviral Responses.ACS nano · 2025Article
- Co-option of mitochondrial nucleic acid-sensing pathways by HSV-1 UL12.5 for reactivation from latent infection.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Nogo-A exacerbates sepsis-associated encephalopathy by modulating microglial SHP-2/NLRP3 balance and inducing ROS and M1 polarization.Biomolecules & biomedicine · 2024Article
- ER-transiting bacterial toxins amplify STING innate immune responses and elicit ER stress.Infection and immunity · 2024Article
- Activation of STING in pancreatic cancer-associated fibroblasts exerts an antitumor effect by enhancing tumor immunity.Scientific reports · 2024Article
70 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
The chemotherapeutic agent 5,6-dimethylxanthenone-4-acetic acid (DMXAA) is a potent inducer of type I IFNs and other cytokines. This ability is essential for its chemotherapeutic benefit in a mouse cancer model and suggests that it might also be useful as an antiviral agent. However, the mechanism underlying DMXAA-induced type I IFNs, including the host proteins involved, remains unclear. Recently, it was reported that the antioxidant N-acetylcysteine (NAC) decreased DMXAA-induced TNF-α and IL-6, suggesting that oxidative stress may play a role. The goal of this study was to identify host proteins involved in DMXAA-dependent signaling and determine how antioxidants modulate this response. We found that expression of IFN-β in response to DMXAA in mouse macrophages requires the mitochondrial and endoplasmic reticulum resident protein STING. Addition of the antioxidant diphenylene iodonium (DPI) diminished DMXAA-induced IFN-β, but this decrease was independent of both the NADPH oxidase, Nox2, and de novo generation of reactive oxygen species. Additionally, IFN-β up-regulation by DMXAA was inhibited by agents that target the mitochondrial electron transport chain and, conversely, loss of mitochondrial membrane potential correlated with diminished innate immune signaling in response to DMXAA. Up-regulation of Ifnb1 gene expression mediated by cyclic dinucleotides was also impaired by DPI, whereas up-regulation of Ifnb1 mRNA due to cytosolic double-stranded DNA was not. Although both stimuli signal through STING, cyclic dinucleotides interact directly with STING, suggesting that recognition of DMXAA by STING may also be mediated by direct interaction.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.