IRAK4在对乙酰氨基酚诱导的急性肝细胞损伤中的作用及其机制

doi:10.3969/j.issn.1004-616x.2022.04.002

Abstract

Abstract: OBJECTIVE: To investigate the role and mechanism of IRAK4 in acute liver cell injury induced by acetaminophen (APAP). METHODS: Human liver cell line L02 cells were divided into control and treatment groups. The latter were treated with 20 mmol/L APAP for 6,12 and 24 hours. Cell viability was detected by CCK-8 method,apoptosis rates were detected by flow cytometry combined with AnnexinV/PI double staining, mitochondrial changes were detected by MitoSOX and JC-1 fluorescence dye, relative expression levels of IRAK4 were detected by fluorescence quantitative PCR (qPCR) and Western blot,L02 cell viability, and apoptosis and mitochondrial reactive oxygen species (mtROS) were detected after silencing the IRAK4 gene. After treatment with 10 mmol/L N-acetylhemionine (NAC) for 24 hours,L02 cell viability was detected by CCK-8 method,and IRAK4 gene expression level was detected by qPCR. RESULTS: Compared with the control group,cell viabilities were reduced and apoptosis rates were significantly increased after the APAP treatment for 24 h (P<0.05). After 12 and 24 h treatments,the levels of mtROS increased significantly (P<0.05);mitochondrial membrane potential decreased significantly at different time points (P<0.05). qPCR and Western blot results showed that IRAK4 expression increased after treatment for 24 h (P<0.05). After silencing IRAK4 gene,compared with the control and APAP groups,cell viability increased,apoptosis decreased and mtROS decreased (P<0.05). Compared with APAP group,NAC treatment increased cell viability and decreased mRNA expression of IRAK4 gene (P<0.05). CONCLUSION: IRAK4 might be involved in APAP-induced acute liver cell injury and would be a therapeutic target of APAP liver cell injury.

Key words: IRAK4, acetaminophen, oxidative stress, liver injury

CLC Number:

R394.6

CAI Jiao, KONG Deqin, LONG Zi, PENG Jie, LIU Jiangzheng, LIU Rui, HAI Chunxu. Role of IRAK4 in acetaminophen-induced acute liver cell injury[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2022, 34(4): 255-261.

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Role of IRAK4 in acetaminophen-induced acute liver cell injury

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