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A cold-inducible RNA-binding protein (CIRP)-derived peptide attenuates inflammation and organ injury in septic mice.

ABSTRACT: Cold-inducible RNA-binding protein (CIRP) is a novel sepsis inflammatory mediator and C23 is a putative CIRP competitive inhibitor. Therefore, we hypothesized that C23 can ameliorate sepsis-associated injury to the lungs and kidneys. First, we confirmed that C23 dose-dependently inhibited TNF-? release, I?B? degradation, and NF-?B nuclear translocation in macrophages stimulated with CIRP. Next, we observed that male C57BL/6 mice treated with C23 (8?mg/kg BW) at 2?h after cecal ligation and puncture (CLP) had lower serum levels of LDH, ALT, IL-6, TNF-?, and IL-1? (reduced by ?39%) at 20?h after CLP compared with mice treated with vehicle. C23-treated mice also had improved lung histology, less TUNEL-positive cells, lower serum levels of creatinine (34%) and BUN (26%), and lower kidney expression of NGAL (50%) and KIM-1 (86%). C23-treated mice also had reduced lung and kidney levels of IL-6, TNF-?, and IL-1?. E-selectin and ICAM-1 mRNA was significantly lower in C23-treated mice. The 10-day survival after CLP of vehicle-treated mice was 55%, while that of C23-treated mice was 85%. In summary, C23 decreased systemic, lung, and kidney injury and inflammation, and improved the survival rate after CLP, suggesting that it may be developed as a new treatment for sepsis.

SUBMITTER: Zhang F

PROVIDER: S-EPMC5809586 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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A cold-inducible RNA-binding protein (CIRP)-derived peptide attenuates inflammation and organ injury in septic mice.

Zhang Fangming F Brenner Max M Yang Weng-Lang WL Wang Ping P

Scientific reports 20180212 1

Cold-inducible RNA-binding protein (CIRP) is a novel sepsis inflammatory mediator and C23 is a putative CIRP competitive inhibitor. Therefore, we hypothesized that C23 can ameliorate sepsis-associated injury to the lungs and kidneys. First, we confirmed that C23 dose-dependently inhibited TNF-α release, IκBα degradation, and NF-κB nuclear translocation in macrophages stimulated with CIRP. Next, we observed that male C57BL/6 mice treated with C23 (8 mg/kg BW) at 2 h after cecal ligation and punct ...[more]

PMID: 29434211

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Project description:Sepsis is a lethal and complex clinical syndrome caused by infection or suspected infection. Cold-inducible RNA-binding protein (CIRP) is a widely distributed cold-shock protein that plays a proinflammatory role in sepsis and that may induce organ damage. However, clinical studies regarding the use of CIRP for the prognostic evaluation of sepsis are lacking. The purpose of this research was to investigate the prognostic significance of peripheral blood concentrations of CIRP in sepsis. Sepsis was assessed using several common measures, including the Acute Physiology and Chronic Health Evaluation II (APACHE II) score; the Sepsis-related Organ Failure Assessment (SOFA) score; the lactate, serum creatinine, and procalcitonin (PCT) levels; the white blood cell (WBC) count; and the neutrophil ratio (N%).Sixty-nine adult patients with sepsis were enrolled in this study. According to the mortality data from the hospital, 38 patients were survivors, and 31 were nonsurvivors. The plasma levels of the biomarkers were measured and the APACHE II and SOFA scores were calculated within 24 hours of patient enrollment into our study. The CIRP level was measured via ELISA.The plasma level of CIRP was significantly higher in the nonsurvivors than in the survivors (median (IQR) 4.99 (2.37-30.17) ng/mL and 1.68 (1.41-13.90) ng/mL, respectively; p = 0.013). The correlations of the CIRP level with the APACHE II score (r = 0.248, p = 0.040, n = 69), the SOFA score (r = 0.323, p = 0.007, n = 69), the serum creatinine level (r = 0.316, p = 0.008, n = 69), and the PCT level (r = 0.282, p = 0.019, n = 69) were significant. Receiver operator characteristic (ROC) curve analysis showed that the area under the ROC curve (AUC) for the CIRP level was 0.674 (p = 0.013). According to Cox proportional hazards models, the CIRP level independently predicts sepsis mortality. When the CIRP level in the peripheral blood increased by 10 ng/mL, the mortality risk increased by 1.05-fold (p = 0.012). Thus, the CIRP level reflects the degree of renal injury but does not predict the severity of sepsis or organ damage.An elevated plasma concentration of CIRP was significantly associated with poor prognosis among patients with sepsis. Therefore, CIRP is a potential predictor of sepsis prognosis.

Dataset Information

A cold-inducible RNA-binding protein (CIRP)-derived peptide attenuates inflammation and organ injury in septic mice.

Publications

A cold-inducible RNA-binding protein (CIRP)-derived peptide attenuates inflammation and organ injury in septic mice.

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