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Cell Physiol Biochem. 2017;43(1):209-222. doi: 10.1159/000480340. Epub 2017 Aug 30.

Involvement of S100A8/A9-TLR4-NLRP3 Inflammasome Pathway in Contrast-Induced Acute Kidney Injury.

Author information

1
Department of Pathology, Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.
2
Clinical Laboratory, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
3
Department of Critical Care Medicine and Emergency, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
4
Department of Medical Genetics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.
5
Department of Physiology, Zhongshan School of Medicine, SunYat-sen University, Guangzhou, China.
6
Department of Nephrology, Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.

Abstract

BACKGROUND:

Contrast-induced acute kidney injury (CIAKI) is a common cause of hospital-acquired acute kidney injury (AKI). S100A8/A9-TLR4-NLRP3 inflammasome pathway triggers inflammation, apoptosis and tissue injury in several AKI models. Nevertheless, the underlying mechanism of S100A8/A9-TLR4-NLRP3 inflammasome pathway in CIKAI is not clear. We aimed to investigate the possible role of S100A8/A9-TLR4-NLRP3 inflammasome in the pathophysiology of CIAKI.

METHODS:

We treated male rats and NRK-52E cells by iopromide to establish in vivo and in vitro models of CIAKI. We collected serum and urine samples to detect renal function. We obtained kidney tissue for histological analysis and detection of protein concentration. We used inhibitor of TLR4 and NLRP3-siRNA to further testify their role in CIAKI in NRK-52E cells.

RESULTS:

Iopromide caused elevation of SCr, BUN and NGAL level, decrease of endogenous creatinine clearance, morphological injury and tubular apoptosis, enhanced IL-1β and IL-18 expression, and increased expression of S100A8/A9, TLR4 and NLRP3 inflammsome. In NRK-52E cells, iopromide caused enhanced apoptotic rates and ROS generation, which could be ameliorated by inhibitor of TLR4 and NLRP3-siRNA. Moreover, inhibition of TLR4 dampened NLRP3 expression.

CONCLUSION:

S100A8/A9-TLR4-NLRP3 inflammasome pathway represented a key mechanism of CI-AKI, which provided a potential therapeutic target.

KEYWORDS:

Acute kidney injury; Contrast medium; NLRP3 inflammasome; S100A8/A9; TLR4

PMID:
28854431
DOI:
10.1159/000480340
[Indexed for MEDLINE]
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