ArticleRedox biology2020
Chemical modification of pro-inflammatory proteins by peroxynitrite increases activation of TLR4 and NF-κB: Implications for the health effects of air pollution and oxidative stress.
Article in Redox biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 55 citations in OpenAlex.
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- Environmental influences on macrophage epigenetics and trained immunity: a review.Molecular biology reports · 2026Review
- In Vitro TLR4 Stimulating Bioactivities of Amylase/Trypsin-Inhibitors from Wheat (Foods (Basel, Switzerland) · 2026Article
- Reactive oxygen species (ROS) in cancer: from mechanism to therapeutic implications.Signal transduction and targeted therapy · 2026Review
- Medicinal Plants That Modulate Nitric Oxide Synthase Activity: Implications in Inflammation and Oxidative Stress.Drug design, development and therapy · 2026Review
- A multifunctional conductive physiomimetic scaffold: synergy of rGO coating and cannabis-derived nanotopography for infection-resistant bone repair.Frontiers in bioengineering and biotechnology · 2026Article
- The Potential Role of Microalgal Antioxidant Molecules on the Microbiota-Gut Axis in Inflammatory Bowel Diseases.Biomolecules · 2025Review
- Effects of iron accumulation and its chelation on oxidative stress in intracortical implants.Acta biomaterialia · 2025Article
- Impact of 4-Environment & health (Washington, D.C.) · 2025Article
- Bridging the gap: Integrating exercise mimicry into chronic disease management through suppressing chronic inflammation.Journal of advanced research · 2025Review
- Long-term exposure to air pollution and gastrointestinal disease: findings from a nationwide cohort study in China.BMC public health · 2025Article
- Advances in the Regulation of Inflammatory Mediators in Nitric Oxide Synthase: Implications for Disease Modulation and Therapeutic Approaches.International journal of molecular sciences · 2025Review
- Global, regional, and national burden of knee osteoarthritis attributable to high BMI: a systematic analysis from 1990 to 2021 and projections to 2050.Frontiers in public health · 2025Article
- Oxidized Melanoma Antigens Promote Activation and Proliferation of Cytotoxic T-Cell Subpopulations.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Low serum double-stranded DNA levels are associated with higher survival rates in severe COPD patients.ERJ open research · 2024Article
- Endogenous Nitric Oxide Can Enhance Oxidative Stress Caused by Air Pollutants and Explain Higher Susceptibility of Individuals with Inflammatory Disorders.Environmental science & technology · 2024Article
- Uric Acid: A Translational Journey in Cerebroprotection That Spanned Preclinical and Human Data.Neurology · 2023Review
- Subchronic exposure to 1,2-naphthoquinone induces adipose tissue inflammation and changes the energy homeostasis of mice, partially due to TNFR1 and TLR4.Toxicology reports · 2023Article
- Intercellular mitochondrial transfer alleviates pyroptosis in dental pulp damage.Cell proliferation · 2023Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Environmental pollutants like fine particulate matter can cause adverse health effects through oxidative stress and inflammation. Reactive oxygen and nitrogen species (ROS/RNS) such as peroxynitrite can chemically modify proteins, but the effects of such modifications on the immune system and human health are not well understood. In the course of inflammatory processes, the Toll-like receptor 4 (TLR4) can sense damage-associated molecular patterns (DAMPs). Here, we investigate how the TLR4 response and pro-inflammatory potential of the proteinous DAMPs α-Synuclein (α-Syn), heat shock protein 60 (HSP60), and high-mobility-group box 1 protein (HMGB1), which are relevant in neurodegenerative and cardiovascular diseases, changes upon chemical modification with peroxynitrite. For the peroxynitrite-modified proteins, we found a strongly enhanced activation of TLR4 and the pro-inflammatory transcription factor NF-κB in stable reporter cell lines as well as increased mRNA expression and secretion of the pro-inflammatory cytokines TNF-α, IL-1β, and IL-8 in human monocytes (THP-1). This enhanced activation of innate immunity via TLR4 is mediated by covalent chemical modifications of the studied DAMPs. Our results show that proteinous DAMPs modified by peroxynitrite more potently amplify inflammation via TLR4 activation than the native DAMPs, and provide first evidence that such modifications can directly enhance innate immune responses via a defined receptor. These findings suggest that environmental pollutants and related ROS/RNS may play a role in promoting acute and chronic inflammatory disorders by structurally modifying the body's own DAMPs. This may have important consequences for chronic neurodegenerative, cardiovascular or gastrointestinal diseases that are prevalent in modern societies, and calls for action, to improve air quality and climate in the Anthropocene.
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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.