Interleukin-27 Ameliorates Renal Ischemia-Reperfusion Injury through Signal Transducers and Activators of Transcription 3 Signaling Pathway
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 deter...
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Published in | Kidney & blood pressure research Vol. 44; no. 6; pp. 1453 - 1464 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
Basel, Switzerland
S. Karger AG
01.12.2019
Karger Publishers |
Subjects | |
Online Access | Get full text |
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Summary: | 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. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1420-4096 1423-0143 |
DOI: | 10.1159/000503923 |