Characterization of the double-stranded RNA responses in human liver progenitor cells

被引：24

作者：

Maire, Magali ^{[1
,2
]}

Parent, Romain ^{[1
,2
]}

Morand, Anne-Laure ^{[1
,2
]}

Alotte, Christine ^{[1
,2
]}

Trepo, Christian ^{[1
,2
,3
]}

Durantel, David ^{[1
,2
]}

Petit, Marie-Anne ^{[1
,2
]}

机构：

[1] INSERM, U 871, F-69003 Lyon, France

[2] Univ Lyon 1, IFR62, F-69008 Lyon, France

[3] Serv Hepatol & Gastroenterol, Hotel Dieu, F-69002 Lyon, France

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2008年 / 368卷 / 03期

关键词：

HepaRG cells; hepatic progenitors; double-stranded RNA; CXC-chemokines; interferon; hepatitis c virus; replication; Microarray; interference RNA; signaling pathways;

D O I：

10.1016/j.bbrc.2008.01.123

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Human HepaRG cells are liver progenitors which possess hepatocyte-like functionality. We investigated the effects of double-stranded (ds) RNA on interferon (IFN)-beta and chemokine (CK) expression in these cells. By microarray and ELISA, we showed strong induction of CXCL10 and interleulin (IL)-8 besides IFN-beta and other CK ligands. RNA interference directed silencing of TLR3, RIG-1, IRF3, NF kappa B or MAP kinases (p38, ERK, JNK) was carried out. Knockdown of all these molecules, except ERK and JNK, blocked IFN-beta production. Both TLR3 and RIG-I are required for CXCL10 expression. Silencing of TLR3 completely impaired the IL-8 expression. dsRNA-conditioned medium from HepaRG cells exerted a drastic antiviral effect in HCV replicons, and in the JFH-1-based HCV production cell culture system. The IFN-beta knockdown in HepaRG cells removed this antiviral effect but did not enhance their capacity to initiate HCV RNA replication. We conclude that dsRNA induces antiviral and pro-inflammatory status in HepaRG cells. (c) 2008 Elsevier Inc. All rights reserved.

引用

页码：556 / 562

页数：7

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