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Role of the nucleotide‐binding domain‐like receptor protein 3 inflammasome in acute kidney injury
Author(s) -
Cao Yanhui,
Fei Dongsheng,
Chen Mingwei,
Sun Miao,
Xu Jun,
Kang Kai,
Jiang Lei,
Zhao Mingyan
Publication year - 2015
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.13379
Subject(s) - inflammasome , proinflammatory cytokine , caspase 1 , downregulation and upregulation , acute kidney injury , inflammation , medicine , interleukin 18 , kidney , innate immune system , immunology , creatinine , receptor , biology , cytokine , biochemistry , gene
Acute kidney injury ( AKI ), which is associated with high mortality rates, involves renal inflammation related to the activation of innate immunity. The inflammatory response in AKI involves the inflammasome, which integrates danger signals into caspase‐1‐activating platforms, leading to the processing and secretion of the proinflammatory cytokines interleukin ( IL )‐1β and IL ‐18. The nucleotide‐binding domain‐like receptor protein 3 ( NLRP 3) inflammasome plays a role in the development of many diseases, including AKI . However, the mechanisms by which the NLRP 3 inflammasome translates different danger signals into the expression of proinflammatory cytokines remain unclear. Here, we investigated the role of the NLRP 3 inflammasome in renal injury in a cecal ligation and puncture ( CLP ) model of sepsis‐induced AKI . CLP decreased blood pressure and increased serum creatinine levels and neutrophil infiltration into the kidney in parallel with the upregulation of NLRP 3, the adaptor protein apoptosis‐associated speck‐like protein, and caspase‐1 expression and activity in kidney tissues, and increases in the serum and kidney levels of IL ‐1β and IL ‐18. Genetic deletion of NLRP3 reversed the CLP ‐induced reduction in blood pressure and increases in serum creatinine level and neutrophil infiltration, and attenuated the CLP ‐induced upregulation of apoptosis‐associated speck‐like protein, caspase‐1 expression and activity, and the secretion of IL ‐1β and IL ‐18, similarly to the effects of caspase‐1 inhibition. Taken together, our results indicate that activation of the NLRP 3 inflammasome contributes to the development of hypotension and the inflammatory response of AKI , suggesting its possible role as a therapeutic target for the treatment of kidney diseases.