乙型肝炎病毒下调肝癌细胞系中的维生素D受体水平，从而防

StephenW

Mol Med. 2018 Oct 16;24(1):53. doi: 10.1186/s10020-018-0055-0.
Hepatitis B virus downregulates vitamin D receptor levels in hepatoma cell lines, thereby preventing vitamin D-dependent inhibition of viral transcription and production.
Gotlieb N1, Tachlytski I1, Lapidot Y1,2, Sultan M1, Safran M1, Ben-Ari Z3,4,5.
Author information

1
    Liver Reaserch Laboratory, Sheba Medical Center, Tel Hashomer, 52620, Ramat Gan, Israel.
2
    The Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
3
    Liver Reaserch Laboratory, Sheba Medical Center, Tel Hashomer, 52620, Ramat Gan, Israel. [email protected].
4
    Liver Disease Center, Sheba Medical Center, Tel Hashomer, 52620, Ramat Gan, Israel. [email protected].
5
    The Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel. [email protected].

Abstract
BACKGROUND:

Vitamin D is a key immune-modulator that plays a role in the innate and adaptive immune systems. Certain pathogens impair the immune defense by downregulating the vitamin D receptor (VDR) pathway. Low serum levels of vitamin D are associated with increased hepatitis B virus (HBV) replication. Our study aimed to assess the in-vitro relationship between HBV production and Vitamin D signaling pathway and to explore the associated mechanism(s).
METHODS:

HBV transcription and replication was evaluated by qRT-PCR of the HBV-RNA and covalently closed circular DNA (cccDNA). Furthermore, we have transfected the 1.3 X HBV-Luc plasmid to the cells and measured the Luciferase activity using Luminometer. Vitamin D signaling pathway activation was evaluated by measuring the expression levels of VDR, CYP24A1, Tumor necrosis factor α (TNFα) and cathelicidin (CAMP) by qRT-PCR. All assays were performed on HepG2.2.15, HepG2, and HepAD38 cells treated with or without Vitamin D active metabolite: calcitriol.
RESULTS:

Calcitriol did not suppress HBV transcription, cccDNA expression or HBV RNA levels in HepG2.2.15 cells. However, VDR transcript levels in HepG2.215 cells were significantly lower compared to HepG2 cells. Similar results were obtained in HepAD38 cell where VDR expression was down-regulated when HBV transcript level was up-regulated. In addition, calcitriol induced VDR-associated signaling, resulting in upregulation of CYP24A1, TNFα and CAMP expression level in HepG2 cells but not in the HepG2.2.15 cells.
CONCLUSIONS:

These findings indicate that VDR expression is downregulated in HBV-transfected cells, thereby preventing vitamin D from inhibiting transcription and translation of HBV in vitro. HBV might use this mechanism to avoid the immunological defense system by affecting both TNFα and CAMP signaling pathways.
KEYWORDS:

Downregulation; Hepatitis B virus (HBV); Immune system; Vitamin D; Vitamin D receptor (VDR)

PMID:
    30326825
DOI:
    10.1186/s10020-018-0055-0

StephenW

Mol Med。 2018年10月16日; 24（1）：53。 doi：10.1186 / s10020-018-0055-0。
乙型肝炎病毒下调肝癌细胞系中的维生素D受体水平，从而防止维生素D依赖性抑制病毒转录和产生。
Gotlieb N1，Tachlytski I1，Lapidot Y1,2，Sultan M1，Safran M1，Ben-Ari Z3,4,5。
作者信息

1
    肝脏研究实验室，Sheba医疗中心，Tel Hashomer，52620，Ramat Gan，以色列。
2
    特拉维夫大学萨克勒医学院，以色列特拉维夫。
3
    肝脏研究实验室，Sheba医疗中心，Tel Hashomer，52620，Ramat Gan，以色列。 [email protected]。
4
    谢巴医疗中心肝病中心，Tel Hashomer，52620，以色列拉马特甘。 [email protected]。
五
    特拉维夫大学萨克勒医学院，以色列特拉维夫。 [email protected]。

抽象
背景：

维生素D是一种关键的免疫调节剂，在先天和适应性免疫系统中发挥作用。某些病原体通过下调维生素D受体（VDR）途径来损害免疫防御。低血清维生素D水平与乙型肝炎病毒（HBV）复制增加有关。我们的研究旨在评估HBV生成与维生素D信号通路之间的体外关系，并探讨相关的机制。
方法：

通过HBV-RNA和共价闭合环状DNA（cccDNA）的qRT-PCR评估HBV转录和复制。此外，我们已将1.3×HBV-Luc质粒转染至细胞并使用发光计测量荧光素酶活性。通过qRT-PCR测量VDR，CYP24A1，肿瘤坏死因子α（TNFα）和导管素（CAMP）的表达水平来评估维生素D信号传导途径的活化。所有测定均在用或不用维生素D活性代谢物：骨化三醇处理的HepG2.2.15，HepG2和HepAD38细胞上进行。
结果：

骨化三醇不抑制HepG2.2.15细胞中的HBV转录，cccDNA表达或HBV RNA水平。然而，与HepG2细胞相比，HepG2.215细胞中的VDR转录物水平显着降低。在HepAD38细胞中获得了类似的结果，其中当HBV转录物水平上调时VDR表达下调。此外，骨化三醇诱导VDR相关信号传导，导致HepG2细胞中CYP24A1，TNFα和CAMP表达水平的上调，但HepG2.2.15细胞中没有。
结论：

这些发现表明VDR表达在HBV转染的细胞中下调，从而阻止维生素D在体外抑制HBV的转录和翻译。 HBV可能通过影响TNFα和CAMP信号通路来利用这种机制来避免免疫防御系统。
关键词：

下调;乙型肝炎病毒（HBV）;免疫系统;维生素D;维生素D受体（VDR）

结论：
    30326825
DOI：
    10.1186 / s10020-018-0055-0

StephenW

https://molmed.biomedcentral.com ... 6/s10020-018-0055-0