ArticleNature medicine2013
Cold-inducible RNA-binding protein (CIRP) triggers inflammatory responses in hemorrhagic shock and sepsis.
Article in Nature medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 282 papers.
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Who cites it
282 citing papers in PubMed, 443 citations in OpenAlex.
- Extracellular CIRP induces neurotoxic astrocytes via TREM-1 in Alzheimer's disease.bioRxiv : the preprint server for biology · 2026Article
- Role of DLL4 in Neutrophil Aging and Impaired Clearance in Sepsis.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- Inhibition of eCIRP Attenuates Inflammation and Gut Injury After Radiation Combined Injury with Sepsis.Medical sciences (Basel, Switzerland) · 2026Article
- Hallmarks of the multidimensional immune response to trauma in humans.Nature immunology · 2026Review
- Phosphodiesterase 4 Inhibitor Roflumilast Ameliorates Polytrauma-Induced Acute Kidney Injury by Attenuating HMGB1 and Renal Inflammatory Pathways in Rats.International journal of molecular sciences · 2026Article
- Inflammatory gut-liver crosstalk: mechanisms and therapeutic targets.Experimental & molecular medicine · 2026Review
- CIRP Promotes Redox-Inflammatory Endothelial Injury in High-Fat Diet-Fed ApoEAntioxidants (Basel, Switzerland) · 2026Article
- Targeting CIRP and IL-6R-mediated microglial inflammation to improve outcomes in intracerebral hemorrhage.Journal of advanced research · 2026Article
- Increased Serum Cold-Inducible RNA-Binding Protein Levels in Psoriasis.Annals of dermatology · 2026Article
- Article
- Radiation-induced eCIRP Causes Alzheimer's Disease-like Neuronal Tau Phosphorylation.Molecular neurobiology · 2026Article
- Article
- Cold exposure increases aortic dissection risk through extracellular cold inducible RNA binding protein and toll like receptor 4 signaling.Scientific reports · 2026Article
- Role of eCIRP in Mediating Post-ischemia Microglial Phagocytosis via TREM-2 Receptor: Insights from Porcine and Mouse Cellular Models.Molecular neurobiology · 2026Article
- Cold inducible RNA binding protein promotes fibroblast activation and its inhibition represents a potential therapeutic target in pulmonary fibrosis.Scientific reports · 2026Article
- The Role of Cold-Inducible RNA-Binding Protein (CIRP) in Neurological Disorders.Brain sciences · 2026Review
- Targeting of CIRP attenuates osteoarthritis progression via suppressing TLR4/NF‑κB/NLRP3 signaling axis.International journal of molecular medicine · 2026Article
- The Dual Role of Natural Killer Cells in the Septic Liver.Journal of inflammation research · 2026Review
- Ionizing radiation and Alzheimer's disease: epidemiology, mechanisms, and eCIRP-mediated tau pathology.Frontiers in immunology · 2026Review
- N-myc and STAT interactor is a novel biomarker for predicting the severity and clinical outcome of sepsis: a prospective research.Frontiers in cellular and infection microbiology · 2026Article
222 more citing papers are in PubMed but not listed here.
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Authors and funding
15 authors at 2 institutions in 2 countries.
Funding
Abstract
A systemic inflammatory response is observed in patients undergoing hemorrhagic shock and sepsis. Here we report increased levels of cold-inducible RNA-binding protein (CIRP) in the blood of individuals admitted to the surgical intensive care unit with hemorrhagic shock. In animal models of hemorrhage and sepsis, CIRP is upregulated in the heart and liver and released into the circulation. In macrophages under hypoxic stress, CIRP translocates from the nucleus to the cytosol and is released. Recombinant CIRP stimulates the release of tumor necrosis factor-α (TNF-α) and HMGB1 from macrophages and induces inflammatory responses and causes tissue injury when injected in vivo. Hemorrhage-induced TNF-α and HMGB1 release and lethality were reduced in CIRP-deficient mice. Blockade of CIRP using antisera to CIRP attenuated inflammatory cytokine release and mortality after hemorrhage and sepsis. The activity of extracellular CIRP is mediated through the Toll-like receptor 4 (TLR4)-myeloid differentiation factor 2 (MD2) complex. Surface plasmon resonance analysis indicated that CIRP binds to the TLR4-MD2 complex, as well as to TLR4 and MD2 individually. In particular, human CIRP amino acid residues 106-125 bind to MD2 with high affinity. Thus, CIRP is a damage-associated molecular pattern molecule that promotes inflammatory responses in shock 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.