| http://purl.uniprot.org/citations/32027619 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/32027619 | http://www.w3.org/2000/01/rdf-schema#comment | "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."xsd:string |
| http://purl.uniprot.org/citations/32027619 | http://purl.org/dc/terms/identifier | "doi:10.1172/jci.insight.133715"xsd:string |
| http://purl.uniprot.org/citations/32027619 | http://purl.uniprot.org/core/author | "Wang P."xsd:string |
| http://purl.uniprot.org/citations/32027619 | http://purl.uniprot.org/core/author | "Zhou M."xsd:string |
| http://purl.uniprot.org/citations/32027619 | http://purl.uniprot.org/core/author | "Ma G."xsd:string |
| http://purl.uniprot.org/citations/32027619 | http://purl.uniprot.org/core/author | "Aziz M."xsd:string |
| http://purl.uniprot.org/citations/32027619 | http://purl.uniprot.org/core/author | "Yen H.T."xsd:string |
| http://purl.uniprot.org/citations/32027619 | http://purl.uniprot.org/core/author | "Denning N.L."xsd:string |
| http://purl.uniprot.org/citations/32027619 | http://purl.uniprot.org/core/date | "2020"xsd:gYear |
| http://purl.uniprot.org/citations/32027619 | http://purl.uniprot.org/core/name | "JCI Insight"xsd:string |
| http://purl.uniprot.org/citations/32027619 | http://purl.uniprot.org/core/pages | "133715"xsd:string |
| http://purl.uniprot.org/citations/32027619 | http://purl.uniprot.org/core/title | "Extracellular CIRP induces macrophage endotoxin tolerance through IL-6R-mediated STAT3 activation."xsd:string |
| http://purl.uniprot.org/citations/32027619 | http://purl.uniprot.org/core/volume | "5"xsd:string |
| http://purl.uniprot.org/citations/32027619 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/32027619 |
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