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http://purl.uniprot.org/citations/33902703http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/33902703http://www.w3.org/2000/01/rdf-schema#comment"

Background

Gout is an autoinflammatory disease driven by interleukin-1 (IL-1) induction in response to uric acid crystals. IL-1β production is dependent on inflammasome activation, which requires a priming signal, followed by an activating signal. The cold-inducible RNA-binding protein (CIRP) has been recently identified as a damage-associated molecular pattern (DAMP). In this study, we evaluated the roles of CIRP in monosodium urate (MSU)-mediated IL-1β secretion using human neutrophils.

Methods

Human neutrophils were stimulated by MSU in the presence or absence of CIRP priming to determine NLRP3 inflammasome activation and subsequent caspase-1 activation and IL-1β production. Cellular supernatants were analyzed by enzyme-linked immunosorbent assay (ELISA) to determine the presence of IL-1β or caspase-1 (p20). The cellular supernatants and lysates were also analyzed by immunoblotting using anti-cleaved IL-1β or anti-cleaved caspase-1 antibodies.

Results

Neither CIRP nor MSU stimulation alone induced sufficient IL-1β secretion from neutrophils. However, MSU stimulation induced IL-1β secretion from CIRP-primed neutrophils in a dose-dependent manner. This MSU-induced IL-1β secretion from CIRP-primed neutrophils was accompanied by the induction of cleaved IL-1β (p17), which was inhibited by the pretreatment of MCC950, a specific inhibitor for NLRP3. Furthermore, cleaved caspase-1 was induced in the cellular lysates of CIRP/MSU-treated neutrophils. Additionally, CIRP stimulation induced the protein expression of pro-IL-1β in neutrophils.

Conclusions

Our data indicate that CIRP, an endogenous stress molecule, triggers uric acid-induced mature IL-1β induction as a priming stimulus for NLRP3 inflammasome in human neutrophils. We propose that CIRP acts as an important proinflammatory stimulant that primes and activates inflammasome and pro-IL-1β processing in response to uric acid in innate immune cells."xsd:string
http://purl.uniprot.org/citations/33902703http://purl.org/dc/terms/identifier"doi:10.1186/s13075-021-02508-9"xsd:string
http://purl.uniprot.org/citations/33902703http://purl.uniprot.org/core/author"Fujita Y."xsd:string
http://purl.uniprot.org/citations/33902703http://purl.uniprot.org/core/author"Kawakami A."xsd:string
http://purl.uniprot.org/citations/33902703http://purl.uniprot.org/core/author"Sato S."xsd:string
http://purl.uniprot.org/citations/33902703http://purl.uniprot.org/core/author"Watanabe H."xsd:string
http://purl.uniprot.org/citations/33902703http://purl.uniprot.org/core/author"Matsumoto H."xsd:string
http://purl.uniprot.org/citations/33902703http://purl.uniprot.org/core/author"Suzuki E."xsd:string
http://purl.uniprot.org/citations/33902703http://purl.uniprot.org/core/author"Asano T."xsd:string
http://purl.uniprot.org/citations/33902703http://purl.uniprot.org/core/author"Yago T."xsd:string
http://purl.uniprot.org/citations/33902703http://purl.uniprot.org/core/author"Matsuoka N."xsd:string
http://purl.uniprot.org/citations/33902703http://purl.uniprot.org/core/author"Migita K."xsd:string
http://purl.uniprot.org/citations/33902703http://purl.uniprot.org/core/author"Temmoku J."xsd:string
http://purl.uniprot.org/citations/33902703http://purl.uniprot.org/core/author"Yashiro-Furuya M."xsd:string
http://purl.uniprot.org/citations/33902703http://purl.uniprot.org/core/date"2021"xsd:gYear
http://purl.uniprot.org/citations/33902703http://purl.uniprot.org/core/name"Arthritis Res Ther"xsd:string
http://purl.uniprot.org/citations/33902703http://purl.uniprot.org/core/pages"128"xsd:string
http://purl.uniprot.org/citations/33902703http://purl.uniprot.org/core/title"Cold-inducible RNA-binding protein (CIRP) potentiates uric acid-induced IL-1beta production."xsd:string
http://purl.uniprot.org/citations/33902703http://purl.uniprot.org/core/volume"23"xsd:string
http://purl.uniprot.org/citations/33902703http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/33902703
http://purl.uniprot.org/citations/33902703http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/33902703
http://purl.uniprot.org/uniprot/#_B4E2A3-mappedCitation-33902703http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/33902703
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