Characterization of the double-stranded RNA responses in human liver progenitor cells.
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-I, IRF3, NFkappaB 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.
Maire
Magali
M
INSERM, U871, 69003 Lyon, France.
Parent
Romain
R
Morand
Anne-Laure
AL
Alotte
Christine
C
Trépo
Christian
C
Durantel
David
D
Petit
Marie-Anne
MA
D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D016174:Hepacivirus / Q000502:physiology*; D022781:Hepatocytes / Q000187:drug effects / Q000276:immunology* / Q000821:virology*; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage*; D011070:Poly I-C / Q000008:administration & dosage*; D012330:RNA, Double-Stranded / Q000276:immunology*; D013234:Stem Cells / Q000187:drug effects / Q000276:immunology* / Q000821:virology*
D016207:Cytokines; D016898:Interferon-alpha; D012330:RNA, Double-Stranded; D011070:Poly I-C