Substitution in Amino Acid 70 of Hepatitis C Virus Core Protein Changes the Adipokine Profile via Toll-Like Receptor 2/4 Signaling

被引:16
|
作者
Uraki, Satoko [1 ]
Tameda, Masahiko [1 ,2 ,3 ]
Sugimoto, Kazushi [1 ,2 ,3 ]
Shiraki, Katsuya [1 ,3 ]
Takei, Yoshiyuki [3 ]
Nobori, Tsutomu [2 ]
Ito, Masaaki [1 ]
机构
[1] Mie Univ, Sch Med, Dept Internal Med 1, Tsu, Mie 5148507, Japan
[2] Mie Univ, Sch Med, Dept Mol & Lab Med, Tsu, Mie 5148507, Japan
[3] Mie Univ, Sch Med, Dept Gastroenterol & Hepatol, Tsu, Mie 5148507, Japan
来源
PLOS ONE | 2015年 / 10卷 / 06期
关键词
RIBAVIRIN COMBINATION THERAPY; NECROSIS-FACTOR-ALPHA; INSULIN-RESISTANCE; GENOTYPE; 1B; IMPORTANT PREDICTOR; HCV GENOTYPE; STEATOSIS; INTERFERON; INFLAMMATION; ASSOCIATION;
D O I
10.1371/journal.pone.0131346
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Background & Aims It has been suggested that amino acid (aa) substitution at position 70 from arginine (70R) to glutamine (70Q) in the genotype 1b hepatitis C virus (HCV) core protein is associated with insulin resistance and worse prognosis. However, the precise mechanism is still unclear. The aim of this study was to investigate the impact of the substitution at position 70 in HCV core protein on adipokine production by murine and human adipocytes. Methods The influence of treatment with HCV core protein (70R or 70Q) on adipokine production by both 3T3-L1 and human adipocytes were examined with real-time PCR and enzyme-linked immunosorbent assay (ELISA), and triglyceride content was also analyzed. The effects of toll-like receptor (TLR) 2/4 inhibition on IL-6 production by 3T3-L1 induced by HCV core protein were examined. Results IL-6 production was significantly increased and adiponectin production was reduced without a change in triglyceride content by treatment with 70Q compared to 70R core protein in both murine and human adipocytes. IL-6 induction of 3T3-L1 cells treated by 70Q HCV core protein was significantly inhibited with anti-TLR2 antibody by 42%, and by TLR4 inhibitor by 40%. Conclusions Our study suggests that extracellular HCV core protein with substitution at position 70 enhanced IL-6 production and reduced adiponectin production from visceral adipose tissue, which can cause insulin resistance, hepatic steatosis, and ultimately development of HCC.
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页数:14
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