ArticleProceedings of the National Academy of Sciences of the United States of America2014
Linkage of inflammation and oxidative stress via release of glutathionylated peroxiredoxin-2, which acts as a danger signal.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 192 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
192 citing papers in PubMed, 2 syntheses or guidelines pooled it, 364 citations in OpenAlex.
- Coenzyme QNutrients · 2022Pooled it
- The Role of Nutrition in COVID-19 Susceptibility and Severity of Disease: A Systematic Review.The Journal of nutrition · 2021Pooled it
- Trial
- Peroxiredoxins in the kidney: a Jekyll and Hyde existence in disease pathogenesis.Renal failure · 2026Review
- PBMC-derived RNA signatures show impaired ability to regulate immune responses in women developing preeclampsia†.Biology of reproduction · 2026Article
- Antibiotic-Induced Genotoxicity: Molecular Mechanisms, Cytogenetic Damage, and Implications for Human Health.International journal of molecular sciences · 2026Review
- Article
- Gut microbiota-driven IL-17/PPAR axis mediates epigallocatechin-induced intestinal repair in weaned lambs.Journal of animal science and biotechnology · 2026Article
- Interaction Between Composite Dietary Antioxidant Index and Alcohol Consumption on Cardiovascular Diseases: NHANES 2005-2018.Clinical cardiology · 2026Article
- Moonlighting Functions of Mammalian Peroxiredoxins in Cellular Signaling.Antioxidants (Basel, Switzerland) · 2026Review
- Green Ethanolic Repercolation ofNutrients · 2026Article
- Transcriptome changes in overweight neutered female dogs undergoing a weight loss program with or without Spirulina (Arthrospira platensis) supplementation.BMC veterinary research · 2026Article
- Article
- Metabolic Adaptation of CD8⁺ T Cells Limits the Efficacy of Fatty Acid Oxidation Inhibition in Type 1 Diabetes.International journal of biological sciences · 2026Article
- 7-Dehydrocholesterol attenuates osteoarthritis by synergistically inhibiting oxidative stress, inflammation, and ferroptosis in macrophages.Frontiers in pharmacology · 2026Article
- Keratin 20 Suppresses Exosomal Secretion of Peroxiredoxin 2 and Ferroptosis in Acute Kidney Injury.Journal of the American Society of Nephrology : JASN · 2026Article
- Article
- Serum peroxiredoxin 2 emerges as a predictive biomarker of poor neurological outcome and delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage: a prospective cohort study.Neurosurgical review · 2025Article
- Postnatal epigenetic differences in calves following transient fetal infection with bovine viral diarrhea virus.BMC genomics · 2025Article
- Unraveling the multifaceted roles of peroxiredoxins in sickle cell anemia: implications in redox and inflammation adaptations.Annals of hematology · 2025Article
132 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 5 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The mechanism by which oxidative stress induces inflammation and vice versa is unclear but is of great importance, being apparently linked to many chronic inflammatory diseases. We show here that inflammatory stimuli induce release of oxidized peroxiredoxin-2 (PRDX2), a ubiquitous redox-active intracellular enzyme. Once released, the extracellular PRDX2 acts as a redox-dependent inflammatory mediator, triggering macrophages to produce and release TNF-α. The oxidative coupling of glutathione (GSH) to PRDX2 cysteine residues (i.e., protein glutathionylation) occurs before or during PRDX2 release, a process central to the regulation of immunity. We identified PRDX2 among the glutathionylated proteins released in vitro by LPS-stimulated macrophages using mass spectrometry proteomic methods. Consistent with being part of an inflammatory cascade, we find that PRDX2 then induces TNF-α release. Unlike classical inflammatory cytokines, PRDX2 release does not reflect LPS-mediated induction of mRNA or protein synthesis; instead, PRDX2 is constitutively present in macrophages, mainly in the reduced form, and is released in the oxidized form on LPS stimulation. Release of PRDX2 is also observed in human embryonic kidney cells treated with TNF-α. Importantly, the PRDX2 substrate thioredoxin (TRX) is also released along with PRDX2, enabling an oxidative cascade that can alter the -SH status of surface proteins and thereby facilitate activation via cytokine and Toll-like receptors. Thus, our findings suggest a model in which the release of PRDX2 and TRX from macrophages can modify the redox status of cell surface receptors and enable induction of inflammatory responses. This pathway warrants further exploration as a potential novel therapeutic target for chronic inflammatory diseases.
Indexed as
Identifiers
What OpenQuestion holds
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.