Characterization of the double-stranded RNA responses in human liver progenitor cells |
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Authors: | Maire Magali Parent Romain Morand Anne-Laure Alotte Christine Trépo Christian Durantel David Petit Marie-Anne |
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Affiliation: | a INSERM, U871, 69003 Lyon, France b Université Lyon 1, IFR62 Lyon-Est, 69008 Lyon, France c Hospices Civils de Lyon, Hôtel Dieu, Service d’Hépatologie et de Gastroentérologie, 69002 Lyon, France |
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Abstract: | Human HepaRG cells are liver progenitors which possess hepatocyte-like functionality. We investigated the effects of double-stranded (ds) RNA on interferon (IFN)-β and chemokine (CK) expression in these cells. By microarray and ELISA, we showed strong induction of CXCL10 and interleulin (IL)-8 besides IFN-β and other CK ligands. RNA interference directed silencing of TLR3, RIG-I, IRF3, NFκB or MAP kinases (p38, ERK, JNK) was carried out. Knockdown of all these molecules, except ERK and JNK, blocked IFN-β 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-β 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. |
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Keywords: | HepaRG cells Hepatic progenitors Double-stranded RNA CXC-chemokines Interferon Hepatitis C virus Replication Microarray Interference RNA Signaling pathways |
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