Association between lipid accumulation and the cannabinoid system in Huh7 cells expressing HCV genes.
Association between lipid accumulation and the cannabinoid system in Huh7 cells expressing HCV genes.
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DOI：
10.3892/ijmm.2011.622
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发表时间：
2011-05
影响因子：
5.4
通讯作者：
Mako Toyoda;A. Kitaoka;Kazuyuki Machida;T. Nishinakagawa;R. Yada;M. Kohjima;Masaki Kato;K. Kotoh
中科院分区：
文献类型：
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作者：
Mako Toyoda;A. Kitaoka;Kazuyuki Machida;T. Nishinakagawa;R. Yada;M. Kohjima;Masaki Kato;K. Kotoh
来自临床和实验室研究的证据表明，大麻素系统的激活对脂肪变性至关重要，特别是在非酒精性脂肪肝疾病中。然而，丙型肝炎病毒（HCV）感染和大麻素系统之间的关联尚未得到很好的研究，目前还不清楚慢性丙型肝炎中的脂肪变性是否通过内源性大麻素/大麻素受体信号通路的激活而发展。在这项研究中，我们研究了大麻素受体（CB 1）的表达和肝脏Huh 7细胞系中的脂质积累，表达HCV基因。我们使用了稳定表达HCV非结构蛋白（NS）3、NS 4、NS 5A和NS 5 B的Huh 7/Rep-FeO-1b细胞，以及Tet-On Core-2细胞，其中HCV核心蛋白表达是可诱导的。与Huh 7细胞相比，Huh 7/Rep-FeO-1b细胞中储存的甘油三酯水平显著更高。此外，IFNα降低HCV后，Huh 7/Rep-FeO-1b细胞中甘油三酯积累和CB 1受体表达下调。此外，CB 1激动剂处理后，脂质积累似乎增加，而CB 1拮抗剂处理后，虽然没有发现显着差异相比，未经处理的细胞。在Tet-On Core-2细胞中，HCV核心蛋白表达的诱导不影响CB 1表达或甘油三酯积累。这项在培养细胞中的研究结果表明，HCV感染可能激活大麻素系统并导致脂肪变性，但核心蛋白本身可能对大麻素系统没有任何影响。
Evidence from clinical and laboratory studies has accumulated indicating that the activation of the cannabinoid system is crucial for steatosis, especially in non-alcoholic fatty liver disease. However, the association between hepatitis C virus (HCV) infection and the cannabinoid system has not been well investigated and it is unclear whether steatosis in chronic hepatitis C develops via activation of the endocannabinoid/cannabinoid receptor signaling pathway. In this study, we examined the expression of a cannabinoid receptor (CB1) and the lipid accumulation in the hepatic Huh7 cell line, expressing HCV genes. We utilized Huh7/Rep-Feo-1b cells stably expressing HCV non-structural proteins (NS) 3, NS4, NS5A, and NS5B, as well as Tet-On Core-2 cells, in which the HCV core protein expression is inducible. Significantly higher levels of stored triglycerides were found in Huh7/Rep-Feo-1b cells compared to Huh7 cells. Also, triglyceride accumulation and CB1 receptor expression were down-regulated in Huh7/Rep-Feo-1b cells after HCV reduction by IFNα. Moreover, lipid accumulation appeared to increase after CB1 agonist treatment, while it decreased after CB1 antagonist treatment, although significant differences were not found compared to untreated cells. In Tet-On Core-2 cells, induction of HCV core protein expression did not affect CB1 expression or triglyceride accumulation. The results of this study in cultured cells suggest that HCV infection may activate the cannabinoid system and precede steatosis, but the core protein by itself may not have any effect on the cannabinoid system.