ArticleJournal of immunology (Baltimore, Md. : 1950)2014
A critical role for human caspase-4 in endotoxin sensitivity.
Article in Journal of immunology (Baltimore, Md. : 1950), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.
What it found
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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.
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Who cites it
75 citing papers in PubMed, 112 citations in OpenAlex.
- Mapping the holonomic signaling network that drives pathological changes in endotoxic shock.Cellular & molecular immunology · 2026Article
- An overview of human inflammasomes: Activation and regulation.Journal of immunology (Baltimore, Md. : 1950) · 2026Review
- Non-apoptotic Regulated Cell Death Mechanisms in Sepsis and their Therapeutic Potential.Inflammation · 2026Review
- NLRP3 inflammasome in cardiovascular diseases: molecular mechanisms and advances in targeted drug research.Frontiers in immunology · 2026Review
- Regulation of inflammatory processes by caspases.Nature reviews. Molecular cell biology · 2025Review
- Molecular mechanisms and regulation of inflammasome activation and signaling: sensing of pathogens and damage molecular patterns.Cellular & molecular immunology · 2025Review
- Cardiolipin inhibits the non-canonical inflammasome by preventing LPS binding to caspase-4/11.The EMBO journal · 2025Article
- New insights into the noncanonical inflammasome point to caspase-4 as a druggable target.Nature reviews. Immunology · 2025Review
- Poking holes in the blood-brain barrier.Immunity · 2024Article
- Article
- Caspase-5: Structure, Pro-Inflammatory Activity and Evolution.Biomolecules · 2024Review
- Article
- Canonical and non-canonical functions of NLRP3.Journal of advanced research · 2023Review
- The NLRP3 inflammasome fires up heme-induced inflammation in hemolytic conditions.Translational research : the journal of laboratory and clinical medicine · 2023Review
- The non-canonical inflammasome activators Caspase-4 and Caspase-5 are differentially regulated during immunosuppression-associated organ damage.Frontiers in immunology · 2023Article
- The subversion of toll-like receptor signaling by bacterial and viral proteases during the development of infectious diseases.Molecular aspects of medicine · 2022Review
- Lipid A Variants Activate Human TLR4 and the Noncanonical Inflammasome Differently and Require the Core Oligosaccharide for Inflammasome Activation.Infection and immunity · 2022Article
- Pyroptosis in development, inflammation and disease.Frontiers in immunology · 2022Review
- Caspase-4 and -5 Biology in the Pathogenesis of Inflammatory Bowel Disease.Frontiers in pharmacology · 2022Review
- Role of non-canonical pyroptosis in sepsis and other inflammatory diseases.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2021Article
15 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
7 authors at 4 institutions in 1 country.
Funding
Abstract
Response to endotoxins is an important part of the organismal reaction to Gram-negative bacteria and plays a critical role in sepsis and septic shock, as well as other conditions such as metabolic endotoxemia. Humans are generally more sensitive to endotoxins when compared with experimental animals such as mice. Inflammatory caspases mediate endotoxin-induced IL-1β secretion and lethality in mice, and caspase-4 is an inflammatory caspase that is found in the human, and not mouse, genome. To test whether caspase-4 is involved in endotoxin sensitivity, we developed a transgenic mouse expressing human caspase-4 in its genomic context. Caspase-4 transgenic mice exhibited significantly higher endotoxin sensitivity, as measured by enhanced cytokine secretion and lethality following LPS challenge. Using bone marrow-derived macrophages, we then observed that caspase-4 can support activation of caspase-1 and secretion of IL-1β and IL-18 in response to priming signals (LPS or Pam3CSK4) alone, without the need for second signals to stimulate the assembly of the inflammasome. These findings indicate that the regulation of caspase-1 activity by human caspase-4 could represent a unique mechanism in humans, as compared with laboratory rodents, and may partially explain the higher sensitivity to endotoxins observed in humans. Regulation of the expression, activation, or activity of caspase-4 therefore represents targets for systemic inflammatory response syndrome, sepsis, septic shock, and related disorders.
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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.