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

Autor: Zena Huang, Xuexian Tan, Chuli Xie, Yan Lin, Jiaqiong Lin, Xiaohe Zheng
Rok vydání: 2017
Předmět:
Contrast medium
0301 basic medicine
Male
Physiology
Inflammasomes
Interleukin-1beta
Contrast Media
Apoptosis
Pharmacology
Kidney
lcsh:Physiology
Rats
Sprague-Dawley
0302 clinical medicine
S100A8/A9
lcsh:QD415-436
TLR4
lcsh:QP1-981
integumentary system
Acute kidney injury
Interleukin-18
Inflammasome
Acute Kidney Injury
medicine.anatomical_structure
030220 oncology & carcinogenesis
Creatinine
Interleukin 18
RNA Interference
medicine.symptom
medicine.drug
Renal function
Inflammation
Cell Line
lcsh:Biochemistry
03 medical and health sciences
NLR Family
Pyrin Domain-Containing 3 Protein
medicine
Animals
Calgranulin B
Calgranulin A
urogenital system
business.industry
Iopromide
medicine.disease
NLRP3 inflammasome
Rats
Toll-Like Receptor 4
Disease Models
Animal
030104 developmental biology
business
Reactive Oxygen Species
Zdroj: Cellular Physiology and Biochemistry, Vol 43, Iss 1, Pp 209-222 (2017)
ISSN: 1421-9778
Popis: 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.
Databáze: OpenAIRE
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