Caspase-11-mediated tubular epithelial pyroptosis underlies contrast-induced acute kidney injury
Contrast-induced acute kidney injury (CI-AKI) is a serious complication in patients after administration of iodinated contrast media and is associated with a significant high risk for severe renal failure and death due to the wholesale necrosis of the tubules and interstitial inflammation. Pyroptosi...
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Published in | Cell death & disease Vol. 9; no. 10; pp. 983 - 13 |
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Main Authors | , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
London
Nature Publishing Group UK
24.09.2018
Springer Nature B.V |
Subjects | |
Online Access | Get full text |
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Summary: | Contrast-induced acute kidney injury (CI-AKI) is a serious complication in patients after administration of iodinated contrast media and is associated with a significant high risk for severe renal failure and death due to the wholesale necrosis of the tubules and interstitial inflammation. Pyroptosis is a form of programmed lytic cell death that is triggered by inflammatory caspases, but little is known about its role in tubular epithelial cell (TEC) death and contrast-induced acute kidney injury. Here we show that systemic exposure to contrast media causes severe tubular epithelial pyroptosis that is mediated by the inflammatory caspases, caspases 4/5 in human TECs, or the murine homolog caspase-11 in mice in vivo and in mouse TECs in vitro. Knockdown of caspase-4/5 preserved human TECs from cell death and reduced the release of mature IL-1β, and in caspase-11-deficient mice, contrast-induced acute kidney injury was abrogated, indicating a central role for caspase-11 in acute kidney injury. In addition, deletion of caspase-11 in TECs reduced Gsdmd cleavage, which is the key process for execution of pyroptosis. These results establish the requisite role of epithelial pyroptosis in contrast-induced acute kidney injury and suggest that epithelial inflammatory caspases are an important therapeutic target for acute kidney injury. |
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ISSN: | 2041-4889 2041-4889 |
DOI: | 10.1038/s41419-018-1023-x |