ArticleMolecular medicine (Cambridge, Mass.)2015
Serum Amyloid A Stimulates PKR Expression and HMGB1 Release Possibly through TLR4/RAGE Receptors.
Article in Molecular medicine (Cambridge, Mass.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 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
30 citing papers in PubMed, 37 citations in OpenAlex.
- Serum amyloid A in HFpEF and cardiometabolic diseases.Basic research in cardiology · 2026Review
- Serum amyloid A: multifaceted roles in inflammation and cellular interactions.Immunologic research · 2025Review
- Pro-Dermcidin as an Emerging Regulator of Innate Immunity in Sepsis.International journal of molecular sciences · 2025Review
- Functional Interactions Between Recombinant Serum Amyloid A1 (SAA1) and Chemokines in Leukocyte Recruitment.International journal of molecular sciences · 2025Review
- Balancing inflammation: the specific roles of serum amyloid A proteins in sterile and infectious diseases.Frontiers in immunology · 2025Article
- Major endothelial damage markers identified from hemadsorption filters derived from treated patients with septic shock - endoplasmic reticulum stress and bikunin may play a role.Frontiers in immunology · 2024Article
- Connexin 43 and Pannexin 1 hemichannels as endogenous regulators of innate immunity in sepsis.Frontiers in immunology · 2024Review
- Serum amyloid A contributes to radiation-induced lung injury by activating macrophages through FPR2/Rac1/NF-κB pathway.International journal of biological sciences · 2024Article
- Serum amyloid A regulates TLR2/4-mediated IFN-β signaling pathway against Marek's disease virus.Virus research · 2023Article
- Identification of procathepsin L (pCTS-L)-neutralizing monoclonal antibodies to treat potentially lethal sepsis.Science advances · 2023Article
- Serum amyloid A and metabolic disease: evidence for a critical role in chronic inflammatory conditions.Frontiers in cardiovascular medicine · 2023Review
- Role of Serum Amyloid A in Abdominal Aortic Aneurysm and Related Cardiovascular Diseases.Biomolecules · 2021Review
- Review
- Serum Amyloid A1/Toll-Like Receptor-4 Axis, an Important Link between Inflammation and Outcome of TBI Patients.Biomedicines · 2021Article
- Protein Kinase R in Bacterial Infections: Friend or Foe?Frontiers in immunology · 2021Review
- Identification of tetranectin-targeting monoclonal antibodies to treat potentially lethal sepsis.Science translational medicine · 2020Article
- Time to Develop Therapeutic Antibodies Against Harmless Proteins Colluding with Sepsis Mediators?ImmunoTargets and therapy · 2020Review
- Article
- Bioassay for Endothelial Damage Mediators Retrieved by Hemoadsorption.Scientific reports · 2019Article
- Dysfunctional high-density lipoprotein activates toll-like receptors via serum amyloid A in vascular smooth muscle cells.Scientific reports · 2019Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Serum amyloid A (SAA) proteins are known to be surrogate markers of sepsis, but their pathogenic roles remain poorly elucidated. Here we provide evidence to support a possible role of SAA as a pathogenic mediator of lethal sepsis. In a subset of septic patients for which serum high mobility group box 1 (HMGB1) levels paralleled the clinical scores, some anti-HMGB1 antibodies detected a 12-kDa protein belonging to the SAA family. In contrast to the most abundant SAA1, human SAA induced double-stranded RNA-activated protein kinase R (PKR) expression and HMGB1 release in the wild-type, but not toll-like receptor 4/receptor for advanced glycation end products (TLR4/RAGE)-deficient, macrophages. Pharmacological inhibition of PKR phosphorylation blocked SAA-induced HMGB1 release, suggesting an important role of PKR in SAA-induced HMGB1 release. In animal models of lethal endotoxemia and sepsis, recombinant SAA exacerbated endotoxemic lethality, whereas SAA-neutralizing immunoglobulins G (IgGs) significantly improved animal survival. Collectively, these findings have suggested SAA as an important mediator of inflammatory diseases. Highlights of this study include: human SAA is possibly only expressed in a subset of septic patients; SAA induces HMGB1 release via TLR4 and RAGE receptors; SAA supplementation worsens the outcome of lethal endotoxemia; whereas SAA-neutralizing antibodies confer protection against lethal endotoxemia and sepsis.
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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.