ArticleCritical care (London, England)2014
Receptor-interacting protein kinase 3 deficiency inhibits immune cell infiltration and attenuates organ injury in sepsis.
Article in Critical care (London, England), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 48 citations in OpenAlex.
- A viable kinase-inactive RIPK3 D143N mouse model reveals its scaffold function in driving TNF-induced inflammatory disorder.Cell death discovery · 2026Article
- Non-apoptotic Regulated Cell Death Mechanisms in Sepsis and their Therapeutic Potential.Inflammation · 2026Review
- Crosstalk Between Cell Death and the cGAS-STING Pathway in Sepsis-Associated Acute Lung Injury.Journal of inflammation research · 2025Review
- Caspase-8 in inflammatory diseases: a potential therapeutic target.Cellular & molecular biology letters · 2024Review
- Review
- Role of necroptosis in kidney health and disease.Nature reviews. Nephrology · 2023Review
- RIPK3 promoter hypermethylation in hepatocytes protects from bile acid-induced inflammation and necroptosis.Cell death & disease · 2023Article
- Pannexin1: insight into inflammatory conditions and its potential involvement in multiple organ dysfunction syndrome.Frontiers in immunology · 2023Review
- Potential therapeutic value of necroptosis inhibitor for the treatment of COVID-19.European journal of medical research · 2022Review
- Regulated necrosis, a proinflammatory cell death, potentially counteracts pathogenic infections.Cell death & disease · 2022Review
- Interferon-γ Preferentially Promotes Necroptosis of Lung Epithelial Cells by Upregulating MLKL.Cells · 2022Article
- Dysregulation of neutrophil death in sepsis.Frontiers in immunology · 2022Review
- Signaling pathways and intervention therapies in sepsis.Signal transduction and targeted therapy · 2021Review
- M1 Macrophages Are More Susceptible to Necroptosis.Journal of cellular immunology · 2021Article
- Hepatic inflammation after burn injury is associated with necroptotic cell death signaling.The journal of trauma and acute care surgery · 2020Article
- Collateral damage: necroptosis in the development of lung injury.American journal of physiology. Lung cellular and molecular physiology · 2020Review
- Necroptosis: a crucial pathogenic mediator of human disease.JCI insight · 2019Review
- Plasma receptor interacting protein kinase-3 levels are associated with acute respiratory distress syndrome in sepsis and trauma: a cohort study.Critical care (London, England) · 2019Article
- RIP kinases as modulators of inflammation and immunity.Nature immunology · 2018Review
- Deficiency of receptor-interacting protein kinase 3 (RIPK3) attenuates inflammation and organ injury in neonatal sepsis.Journal of pediatric surgery · 2018Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
introductionSepsis is defined as a systemic hyper-inflammatory immune response, with a subsequent immune-suppressive phase, which leads to multiple organ dysfunction and late lethality. Receptor-interacting protein kinase 3 (RIPK3)-dependent necrosis is implicated in driving tumor necrosis factor alpha (TNF-α)- and sepsis-induced mortality in mice. However, it is unknown if RIPK3 deficiency has any impact on immune cell trafficking, which contributes to organ damage in sepsis.
methodsTo study this, male wild-type (WT) and RIPK3-deficient (Ripk3-/-) mice on C57BL/6 background were subjected to sham operation or cecal ligation and puncture (CLP)-induced sepsis. Blood and tissue samples were collected 20 hours post-CLP for various measurements.
resultsIn our severe sepsis model, the mean survival time of Ripk3-/- mice was significantly extended to 68 hours compared to 41 hours for WT mice. Ripk3-/- mice had significantly decreased plasma levels of TNF-α and IL-6 and organ injury markers compared to WT mice post-CLP. In the lungs, Ripk3-/- mice preserved better integrity of microscopic structure with reduced apoptosis, and decreased levels of IL-6, macrophage inflammatory protein (MIP)-2 and keratinocyte-derived chemokine (KC), compared to WT. In the liver, the levels of MIP-1, MIP-2 and KC were also decreased in septic Ripk3-/- mice. Particularly, the total number of neutrophils in the lungs and liver of Ripk3-/- mice decreased by 59.9% and 66.7%, respectively, compared to WT mice post-CLP. In addition, the number of natural killer (NK) and CD8T cells in the liver decreased by 64.8% and 53.4%, respectively, in Ripk3-/- mice compared to WT mice post-sepsis.
conclusionsOur data suggest that RIPK3 deficiency modestly protected from CLP-induced severe sepsis and altered the immune cell trafficking in an organ-specific manner attenuating organ injury. Thus, RIPK3 acts as a detrimental factor in contributing to the organ deterioration in sepsis.
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