ArticleJCI insight2020
Extracellular CIRP induces macrophage endotoxin tolerance through IL-6R-mediated STAT3 activation.
Article in JCI insight, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
39 citing papers in PubMed, 58 citations in OpenAlex.
- 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
- Histone H3K27 demethylation drives Crohn's disease inflammation: GSK-J4 as a potential epigenetic therapy.Clinical epigenetics · 2026Article
- Article
- The circ_0042103/TAF15/NER axis regulates inflammation and DNA damage in pulpitis.Stem cell research & therapy · 2026Article
- Ionizing radiation and Alzheimer's disease: epidemiology, mechanisms, and eCIRP-mediated tau pathology.Frontiers in immunology · 2026Review
- Cold-Induced RNA-Binding Protein (CIRP) Affects Cerebral Ischemia-Reperfusion Injury Through NF-κB Pathway.Molecular neurobiology · 2025Article
- Unraveling immunosenescence in sepsis: from cellular mechanisms to therapeutics.Cell death & disease · 2025Review
- Extracellular Cold-Inducible RNA-Binding Protein: Progress from Discovery to Present.International journal of molecular sciences · 2025Review
- Intracellular CIRP promotes liver regeneration via STAT3 signaling pathway activation after partial hepatectomy in mice.International journal of molecular medicine · 2025Article
- The role of natural products targeting macrophage polarization in sepsis-induced lung injury.Chinese medicine · 2025Review
- Extracellular cold-inducible RNA-binding protein in CNS injury: molecular insights and therapeutic approaches.Journal of neuroinflammation · 2025Review
- Endotoxin tolerance inhibits NLRP3 inflammasome activation in macrophages of septic mice by restoring autophagic flux through TRIM26.Open medicine (Warsaw, Poland) · 2025Article
- Extracellular CIRP augments inflammation in acute kidney injury via NKG2D-positive macrophages.Frontiers in immunology · 2025Article
- Radiation-induced eCIRP impairs macrophage bacterial phagocytosis.Journal of leukocyte biology · 2024Article
- Traumatic inflammatory response: pathophysiological role and clinical value of cytokines.European journal of trauma and emergency surgery : official publication of the European Trauma Society · 2024Review
- Article
- BMAL2 promotes eCIRP-induced macrophage endotoxin tolerance.Frontiers in immunology · 2024Article
- BMAL2 promotes eCIRP-induced macrophage endotoxin tolerance.Frontiers in immunology · 2024Article
- Promising results of a clinical feasibility study: CIRBP as a potential biomarker in pediatric cardiac surgery.Frontiers in cardiovascular medicine · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Extracellular cold-inducible RNA-binding protein (eCIRP) is a damage-associated molecular pattern, whose effect on macrophages is not entirely elucidated. Here we identified that eCIRP promotes macrophage endotoxin tolerance. Septic mice had higher serum levels of eCIRP; this was associated with a reduced ex vivo immune response of their splenocytes to LPS. Pretreatment of macrophages with recombinant murine CIRP (rmCIRP) resulted in a tolerance to LPS stimulation as demonstrated by a reduction of TNF-α production. We found that eCIRP increased phosphorylated STAT3 (p-STAT3) in macrophages. A STAT3 inhibitor, Stattic, rescued macrophages from rmCIRP-induced tolerance by restoring the release of TNF-α in response to LPS stimulation. We discovered strong binding affinity between eCIRP and IL-6 receptor (IL-6R) as revealed by Biacore, fluorescence resonance energy transfer (FRET), and their colocalization in macrophages by immunostaining assays. Blockade of IL-6R with its neutralizing Ab inhibited eCIRP-induced p-STAT3 and restored LPS-stimulated TNF-α release in macrophages. Incubation of macrophages with rmCIRP skewed them toward an M2 phenotype, while treatment with anti-IL-6R Ab prevented rmCIRP-induced M2 polarization. Thus, we have demonstrated that eCIRP activates p-STAT3 via a novel receptor, IL-6R, to promote macrophage endotoxin tolerance. Targeting eCIRP appears to be a new therapeutic option to correct immune tolerance in sepsis.
Indexed as
Identifiers
What OpenQuestion holds
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.