title: Role of the nucleotide-binding domain-like receptor protein 3 inflammasome in acute kidney injury.
abstract: 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 (NLRP3) inflammasome plays a role in the development of many diseases, including AKI. However, the mechanisms by which the NLRP3 inflammasome translates different danger signals into the expression of proinflammatory cytokines remain unclear. Here, we investigated the role of the NLRP3 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 NLRP3, 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 NLRP3 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.
authors.affiliation: Department of ICU, The First Affiliated Hospital of Harbin Medical University, Heilongjiang Province, China.
authors.forename: Yanhui
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Department of ICU, The First Affiliated Hospital of Harbin Medical University, Heilongjiang Province, China.
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Fei
authors.affiliation: Department of Anatomy, The First Affiliated Hospital of Harbin Medical University, Heilongjiang Province, China.
authors.forename: Mingwei
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Medical Records, The First Affiliated Hospital of Harbin Medical University, Heilongjiang Province, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Sun
authors.affiliation: Department of Orthopaedics, The Second Affiliated Hospital of Harbin Medical University, Heilongjiang Province, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of ICU, The First Affiliated Hospital of Harbin Medical University, Heilongjiang Province, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Kang
authors.affiliation: Department of ICU, The First Affiliated Hospital of Harbin Medical University, Heilongjiang Province, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Department of ICU, The First Affiliated Hospital of Harbin Medical University, Heilongjiang Province, China.
authors.forename: Mingyan
authors.initials: M
authors.lastname: Zhao
mesh_terms: D058186:Acute Kidney Injury / Q000378:metabolism / Q000503:physiopathology*; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D053468:CARD Signaling Adaptor Proteins; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D020170:Caspase 1 / Q000378:metabolism; D003404:Creatinine / Q000097:blood; D004195:Disease Models, Animal; D058847:Inflammasomes / Q000378:metabolism*; D020382:Interleukin-18 / Q000097:blood / Q000378:metabolism; D053583:Interleukin-1beta / Q000097:blood / Q000378:metabolism; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D009504:Neutrophils / Q000473:pathology
chemical_list: D051017:Apoptosis Regulatory Proteins; D053468:CARD Signaling Adaptor Proteins; D002352:Carrier Proteins; C587672:IL1B protein, mouse; D058847:Inflammasomes; D020382:Interleukin-18; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; C498534:Pycard protein, mouse; D003404:Creatinine; D020170:Caspase 1
keywords: acute kidney injury; apoptosis-associated speck-like protein; caspase-1; cecal ligation and puncture; nucleotide-binding domain-like receptor protein 3