ArticleEMBO molecular medicine2020
Glutathione peroxidase 8 negatively regulates caspase-4/11 to protect against colitis.
Article in EMBO molecular medicine, 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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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.
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Who cites it
33 citing papers in PubMed, 52 citations in OpenAlex.
- Targeting of Gpx8-CSF1 axis resets the immune milieu of lung tumor and overcomes resistance to anti-PD-1 therapy.Cell death and differentiation · 2026Article
- Multifaceted regulation of immune cells in radiation-induced pulmonary fibrosis: from mechanistic insights to targeted therapies.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- Expression patterns of glutathione peroxidases family members during tooth development.Journal of molecular histology · 2026Article
- The protective effects of selenium against NLRP3-mediated inflammation and pyroptosis: mechanisms and the potential health benefits.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2026Review
- Taraxacum alleviates ulcerative colitis, accompanied by the modulation of gut microbiota and restoration of intestinal barrier integrity.Frontiers in cellular and infection microbiology · 2026Article
- ZAKα Induces Pyroptosis of Colonic Epithelium Via the Caspase-11/GSDMD Pathway to Aggravate Colitis.Inflammation · 2025Article
- Stress Management: How the Endoplasmic Reticulum Mitigates Protein Misfolding and Oxidative Stress by the Dual Role of Glutathione Peroxidase 8.Biomolecules · 2025Review
- Engineered endoplasmic reticulum-targeting nanodrugs with Piezo1 inhibition and promotion of cell uptake for subarachnoid hemorrhage inflammation repair.Journal of nanobiotechnology · 2025Article
- Tumor microenvironment regulation by reactive oxygen species-mediated inflammasome activation.Archives of pharmacal research · 2025Review
- Article
- Identification and Experimental Validation of Oxidative Stress-Related Biomarkers in Ulcerative Colitis Using Machine Learning.Journal of inflammation research · 2025Article
- Exploring Pyroptosis-related Signature Genes and Potential Drugs in Ulcerative Colitis by Transcriptome Data and Animal Experimental Validation.Inflammation · 2024Article
- GPX8 deficiency-induced oxidative stress reprogrammed m6A epitranscriptome of oral cancer cells.Epigenetics · 2023Article
- SENP2 restrains the generation of pathogenic Th17 cells in mouse models of colitis.Communications biology · 2023Article
- Upregulation of non-canonical and canonical inflammasome genes associates with pathological features in Krabbe disease and related disorders.Human molecular genetics · 2023Article
- GPX8 regulates clear cell renal cell carcinoma tumorigenesis through promoting lipogenesis by NNMT.Journal of experimental & clinical cancer research : CR · 2023Article
- Molecular Characteristics of Cell Pyroptosis and Its Inhibitors: A Review of Activation, Regulation, and Inhibitors.International journal of molecular sciences · 2022Review
- Regulation of ferroptosis by noncoding RNAs: a novel promise treatment in esophageal squamous cell carcinoma.Molecular and cellular biochemistry · 2022Review
- Mechanisms and Consequences of Noncanonical Inflammasome-Mediated Pyroptosis.Journal of molecular biology · 2022Review
- Chosen Antioxidant Enzymes GPx4 and GPx8 in Human Colorectal Carcinoma: Study of the Slovak Population.Medicina (Kaunas, Lithuania) · 2022Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Human caspase-4 and its mouse homolog caspase-11 are receptors for cytoplasmic lipopolysaccharide. Activation of the caspase-4/11-dependent NLRP3 inflammasome is required for innate defense and endotoxic shock, but how caspase-4/11 is modulated remains unclear. Here, we show that mice lacking the oxidative stress sensor glutathione peroxidase 8 (GPx8) are more susceptible to colitis and endotoxic shock, and exhibit reduced richness and diversity of the gut microbiome. C57BL/6 mice that underwent adoptive cell transfer of GPx8-deficient macrophages displayed a similar phenotype of enhanced colitis, indicating a critical role of GPx8 in macrophages. GPx8 binds covalently to caspase-4/11 via disulfide bonding between cysteine 79 of GPx8 and cysteine 118 of caspase-4 and thus restrains caspase-4/11 activation, while GPx8 deficiency leads to caspase-4/11-induced inflammation during colitis and septic shock. Inhibition of caspase-4/11 activation with small molecules reduces the severity of colitis in GPx8-deficient mice. Notably, colonic tissues from patients with ulcerative colitis display low levels of Gpx8 and high caspase-4 expression. In conclusion, these results suggest that GPx8 protects against colitis by negatively regulating caspase-4/11 activity.
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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.