ArticleJournal of immunology (Baltimore, Md. : 1950)2010
NADPH oxidase-dependent reactive oxygen species mediate amplified TLR4 signaling and sepsis-induced mortality in Nrf2-deficient mice.
Article in Journal of immunology (Baltimore, Md. : 1950), 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 111 papers.
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
111 citing papers in PubMed, 189 citations in OpenAlex.
- Programmable ROS modulation by nanomedicine for rheumatoid arthritis treatment.Materials today. Bio · 2026Review
- Oxidative stress-driven disease-associated microglia (DAM)-like polarization in human microglia (HMC3) cells exposed to small-size silver nanoparticles in a transwell co-culture system with neurons (cholinergic differentiated SH-SY5Y) cells in vitro.Archives of toxicology · 2026Article
- Current Insights into Glutathione Depletion in Adult Septic Patients.Antioxidants (Basel, Switzerland) · 2025Review
- On the utility of immobilized phenylarsine oxide in the study of redox sensitive cardiac proteins.Scientific reports · 2025Article
- The Role of NADPH Oxidase 2 in Leukocytes.Antioxidants (Basel, Switzerland) · 2025Review
- Role of oxidative stress in post-burn wound healing.Burns & trauma · 2025Review
- Clinical associations and potential cellular mechanisms linking G6PD deficiency and atherosclerotic cardiovascular disease.npj metabolic health and disease · 2025Review
- MnTheranostics · 2025Article
- 2,4'-Dihydroxybenzophenone: A Promising Anti-Inflammatory Agent Targeting Toll-like Receptor 4/Myeloid Differentiation Factor 2-Mediated Mitochondrial Reactive Oxygen Species Production during Lipopolysaccharide-Induced Systemic Inflammation.ACS pharmacology & translational science · 2024Article
- Supplementing Ryegrass Ameliorates Commercial Diet-Induced Gut Microbial Dysbiosis-Associated Spleen Dysfunctions by Gut-Microbiota-Spleen Axis.Nutrients · 2024Article
- Protective Role of MAVS Signaling for Murine Lipopolysaccharide-Induced Acute Kidney Injury.ImmunoHorizons · 2024Article
- Metabolism-driven glycosylation represents therapeutic opportunities in interstitial lung diseases.Frontiers in immunology · 2024Review
- Ferroptosisand Its Role in the Treatment of Sepsis-Related Organ Injury: Mechanisms and Potential Therapeutic Approaches.Infection and drug resistance · 2024Review
- Transcription Factor NRF2 in Shaping Myeloid Cell Differentiation and Function.Advances in experimental medicine and biology · 2024Review
- Activation of the pentose phosphate pathway in macrophages is crucial for granuloma formation in sarcoidosis.The Journal of clinical investigation · 2023Article
- Reactive oxygen species (ROS) scavenging biomaterials for anti-inflammatory diseases: from mechanism to therapy.Journal of hematology & oncology · 2023Review
- Reactive Oxygen Species and Strategies for Antioxidant Intervention in Acute Respiratory Distress Syndrome.Antioxidants (Basel, Switzerland) · 2023Review
- Lansoprazole attenuates cyclophosphamide-induced cardiopulmonary injury by modulating redox-sensitive pathways and inflammation.Molecular and cellular biochemistry · 2023Article
- Extracellular tau stimulates phagocytosis of living neurons by activated microglia via Toll-like 4 receptor-NLRP3 inflammasome-caspase-1 signalling axis.Scientific reports · 2023Article
- Transcutaneous Electrical Acupoint Stimulation Improves Postoperative Sleep Quality in Patients Undergoing Laparoscopic Gastrointestinal Tumor Surgery: A Prospective, Randomized Controlled Trial.Pain and therapy · 2023Article
51 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
4 authors at 2 institutions in 1 country.
Funding
Abstract
Sepsis syndrome is characterized by a dysregulated inflammatory response to infection. NADPH oxidase-dependent reactive oxygen species (ROS) play significant roles in the pathophysiology of sepsis. We previously showed that disruption of Nrf2, a master regulator of antioxidant defenses, caused a dysregulation of innate immune response that resulted in greater mortality in a polymicrobial sepsis and LPS shock model; however, the underlying mechanisms are unclear. In the current study, compared with wild-type (Nrf2(+/+)) macrophages, we observed greater protein kinase C-induced NADPH oxidase-dependent ROS generation in Nrf2-disrupted (Nrf2(-/-)) macrophages that was modulated by glutathione levels. To address the NADPH oxidase-mediated hyperinflammatory response and sepsis-induced lung injury and mortality in Nrf2(-/-) mice, we used double knockout mice lacking Nrf2 and NADPH oxidase subunit, gp91(phox) (Nrf2(-/-)//gp91(phox-/-)). Compared with Nrf2(+/+) macrophages, LPS induced greater activation of TLR4 as evident by TLR4 surface trafficking and downstream recruitment of MyD88 and Toll/IL-1R domain-containing adaptor in Nrf2(-/-) macrophages that was diminished by ablation of gp91(phox). Similarly, phosphorylation of IkappaB and IFN regulatory factor 3 as well as cytokine expression was markedly higher in Nrf2(-/-) macrophages; whereas, it was similar in Nrf2(+/+) and Nrf2(-/-)//gp91(phox-/-). In vivo studies showed greater LPS-induced pulmonary inflammation in Nrf2(-/-) mice that was significantly reduced by ablation of gp91(phox). Furthermore, LPS shock and polymicrobial sepsis induced early and greater mortality in Nrf2(-/-) mice; whereas, Nrf2(-/-)//gp91(phox-/-) showed prolonged survival. Together, these results demonstrate that Nrf2 is essential for the regulation of NADPH oxidase-dependent ROS-mediated TLR4 activation and lethal innate immune response in sepsis.
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.