Cold-inducible RNA-binding protein potentiates uric acid-induced IL-1[beta] production

• Published in: Arthritis research & therapy Vol. 23; no. 1
• Main Authors: Fujita, Yuya, Yago, Toru, Matsumoto, Haruki, Asano, Tomoyuki, Matsuoka, Naoki, Temmoku, Jumpei, Sato, Shuzo, Yashiro-Furuya, Makiko, Suzuki, Eiji, Watanabe, Hiroshi, Kawakami, Atsushi, Migita, Kiyoshi
• Format: Journal Article
• Language: English
• Published: BioMed Central Ltd 26.04.2021
• Subjects: Binding proteins; Development and progression; Genetic aspects; Gout; Health aspects; Interleukin-1; RNA; Uric acid; Japan
• ISSN: 1478-6354; 1478-6362
• DOI: 10.1186/s13075-021-02508-9

Background Gout is an autoinflammatory disease driven by interleukin-1 (IL-1) induction in response to uric acid crystals. IL-1[beta] 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-1[beta] 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-1[beta] production. Cellular supernatants were analyzed by enzyme-linked immunosorbent assay (ELISA) to determine the presence of IL-1[beta] or caspase-1 (p20). The cellular supernatants and lysates were also analyzed by immunoblotting using anti-cleaved IL-1[beta] or anti-cleaved caspase-1 antibodies. Results Neither CIRP nor MSU stimulation alone induced sufficient IL-1[beta] secretion from neutrophils. However, MSU stimulation induced IL-1[beta] secretion from CIRP-primed neutrophils in a dose-dependent manner. This MSU-induced IL-1[beta] secretion from CIRP-primed neutrophils was accompanied by the induction of cleaved IL-1[beta] (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-1[beta] in neutrophils. Conclusions Our data indicate that CIRP, an endogenous stress molecule, triggers uric acid-induced mature IL-1[beta] 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-1[beta] processing in response to uric acid in innate immune cells.