Interleukin-27 Ameliorates Renal Ischemia-Reperfusion Injury through Signal Transducers and Activators of Transcription 3 Signaling Pathway

• Published in: Kidney & blood pressure research Vol. 44; no. 6; pp. 1453 - 1464
• Main Authors: Zhou, Peihui, Deng, Bo, Wu, Ming, Ding, Feng, Wang, Li
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland S. Karger AG 01.12.2019; Karger Publishers
• Subjects: acute kidney injury; Apoptosis; Arthritis; BAX protein; Bcl-2 protein; Caspase-3; Creatinine; Cytokines; Epithelial cells; Epstein-Barr virus; Flow cytometry; Gene expression; Glycoprotein gp130; Health services; Inflammation; Injuries; Interleukin 12; Interleukin 27; Interleukin 6; Interleukins; Ischemia; Kidneys; Morbidity; Polymerase chain reaction; Proteins; Receptors; renal ischemia-reperfusion injury; Reperfusion; Research Article; signal transducer and activator of transcription 3; Signal transduction; Stat3 protein; Structure-function relationships; Transcription factors; Transducers; Viruses; United States > US; China; Interleukin-27; Acute kidney injury; Renal ischemia-reperfusion injury; Signal transducer and activator of transcription 3; Apoptosis
• ISSN: 1420-4096; 1423-0143
• DOI: 10.1159/000503923

Background: Acute kidney injury (AKI) is a clinical syndrome characterized by significant morbidity and a high death rate. Interleukin (IL)-27 is a newly described member of the IL-6/IL-12 heterodimeric cytokine family and displays anti-inflammatory and antiapoptotic properties. Objectives: To determine the effect and mechanism of IL-27 in AKI. Method: We used a mouse model of renal ischemia/reperfusion (I/R) injury to investigate whether IL-27 has a therapeutic potential for the treatment of AKI. For the IL-27 administration group, IL-27 protein was injected 1 h before ischemia. Human proximal tubular epithelial cells were exposed to ischemia for 2 h and followed by 2 h of reperfusion (I2h+R2h treatment) used as an in vitro model to investigate the effect of IL-27. Results: Two IL-27 subunits, Epstein-Barr virus gene 3 and p28, were upregulated in kidneys 24 h after I/R. Renal expression of IL-27 receptor subunits (gp130 and WSX-1) was also increased. Treatment with IL-27 reduced structural/functional damages, ameliorated renal inflammation, inhibited the cleaved caspase-3 expression, upregulated antiapoptotic protein Bcl-2 and downregulated proapoptotic protein Bax in the kidneys of mice subjected to I/R. Meanwhile, the level of IL-27 receptor on renal tubular epithelial cells was increased after I2h+R2h treatment, and IL-27 administration suppressed I2h+R2h-induced epithelial cell apoptosis. Furthermore, IL-27 treatment led to activation of signal transducer and activator of transcription 3 (STAT3) both in vivo and in vitro, and IL-27-mediated protection against I2h+R2h injury was abolished by STAT3 inhibition. Conclusions: IL-27 protects against renal I/R injury by activating STAT3, suggesting that IL-27 may represent a novel strategy for the treatment of AKI.