ArticleFrontiers in immunology2018
GSKJ4 Protects Mice Against Early Sepsis via Reducing Proinflammatory Factors and Up-Regulating MiR-146a.
Article in Frontiers in immunology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 2 of them syntheses that pooled it.
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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
30 citing papers in PubMed, 2 syntheses or guidelines pooled it, 50 citations in OpenAlex.
- Epigenetic mechanisms of Immune remodeling in sepsis: targeting histone modification.Cell death & disease · 2023Pooled it
- Expression of MicroRNAs in Sepsis-Related Organ Dysfunction: A Systematic Review.International journal of molecular sciences · 2022Pooled it
- Epigenetic regulation of neutrophil dysfunction in sepsis: mechanisms, biomarkers, and translational challenges.Journal of translational medicine · 2026Review
- JMJD3-driven epigenetic reprogramming of p16Bone research · 2026Article
- Histone H3K27 demethylation drives Crohn's disease inflammation: GSK-J4 as a potential epigenetic therapy.Clinical epigenetics · 2026Article
- Gut Microbiota-Non-Coding RNA Axis in Immune Modulation and Disease: From Mechanisms to Clinical Translation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Temporal transcriptional dynamics in cutaneous leishmaniasis reveal novel targets for therapeutic interventions in a dermal mouse model.Frontiers in immunology · 2026Article
- Epigenetic regulation of TIMP-3 expression in human macrophages via physiological and pharmacological modification of histone3 lysine27 (H3K27).Molecular biology reports · 2025Article
- Interaction between stromal cells and tumor cells promotes GCB-DLBCL cell survival via the CD40/RANK-KDM6B-NF-κB axis.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Liver injury in sepsis: manifestations, mechanisms and emerging therapeutic strategies.Frontiers in immunology · 2025Review
- Predicting microRNAs and their Target Genes Involved in Sepsis Pathogenesis by using Bioinformatics Methods.Current pharmaceutical design · 2025Article
- Emerging role of Jumonji domain-containing protein D3 in inflammatory diseases.Journal of pharmaceutical analysis · 2024Review
- α-Ketoglutarate-Dependent KDM6 Histone Demethylases and Interferon-Stimulated Gene Expression in Lupus.Arthritis & rheumatology (Hoboken, N.J.) · 2024Article
- Advances in the Study of Immunosuppressive Mechanisms in Sepsis.Journal of inflammation research · 2023Review
- Mechanisms and application strategies of miRNA‑146a regulating inflammation and fibrosis at molecular and cellular levels (Review).International journal of molecular medicine · 2023Review
- H3K27 tri-demethylase JMJD3 inhibits macrophage apoptosis by promoting ADORA2A in lipopolysaccharide-induced acute lung injury.Cell death discovery · 2022Article
- Therapeutic potential of inhibiting histone 3 lysine 27 demethylases: a review of the literature.Clinical epigenetics · 2022Review
- Opioids and Sepsis: Elucidating the Role of the Microbiome and microRNA-146.International journal of molecular sciences · 2022Review
- Article
- Modes of action and diagnostic value of miRNAs in sepsis.Frontiers in immunology · 2022Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sepsis, defined as life-threatening organ dysfunction, is one of the most common causes of mortality in intensive care units with limited therapeutic options. However, the mechanism underlying the regulation of epigenetics on sepsis remains largely undefined. Here we showed that JMJD3, the histone lysine demethylase, played a critical role in the epigenetic regulation of innate immunity during early sepsis. Pharmacological inhibition of JMJD3 by GSKJ4 protected mice against early septic death and reduced pro-inflammatory cytokine interleukin-1β (IL-1β) production as well as IL-6, tumor necrosis factor-α (TNF-α), and monocyte chemotactic protein-1 (MCP-1) expression. Interestingly, GSKJ4 up-regulated the transcription of anti-inflammatory microRNA-146a (miR-146a) in peritoneal macrophages from septic mice. Mechanistically, JMJD3 negatively regulated the transcription of miR-146a via its demethylation of H3K27me3 on the promoter of miR-146a. Moreover, the transcription of miR-146a was positively regulated by nuclear factor-κB (NF-κB) p65. Inhibition of NF-κB p65 promoted JMJD3 binding to miR-146a promoter and decreased the tri-methylation level of H3K27, while the inhibition of JMJD3 did not affect the recruitment of NF-κB p65 to miR-146a promoter. These results highlight an epigenetic mechanism by which JMJD3 was inhibited by NF-κB p65 from binding to miR-146a promoter to promote the anti-inflammatory response. Taken together, our findings uncover a key role for JMJD3 in modulating the miR-146a transcription and shed light on the JMJD3 inhibitors could be potential therapeutic agents for early sepsis therapy.
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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.