Interleukin-4 induces human hepatocyte apoptosis through a Fas-independent pathway

IL-4 is overexpressed in liver grafts during severe recurrent hepatitis C and rejection. Hepatocyte apoptosis is involved in both these phenomena. We therefore examined the proapoptotic effect of IL-4 on HepG2 cells and human hepatocytes in vitro, together with the underlying mechanisms. We first me...

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Bibliographic Details
Published in:The FASEB journal 2007-05, Vol.21 (7), p.1433-1444
Main Authors: Aoudjehane, Lynda, Podevin, Philippe, Scatton, Olivier, Jaffray, Patrick, Dusanter-Fourt, Isabelle, Feldmann, Gérard, Massault, Pierre-Philippe, Grira, Lilia, Bringuier, Annie, Dousset, Bertrand, Chouzenoux, Sandrine, Soubrane, Olivier, Calmus, Yvon, Conti, Filomena
Format: Article
Language:English
Subjects:
Apoptosis - drug effects
Base Sequence
Caspases - metabolism
Cell Line, Tumor
DNA Primers
Electrophoretic Mobility Shift Assay
fas Receptor - metabolism
Flow Cytometry
Hepatocytes - cytology
Hepatocytes - drug effects
Humans
IL-4
Immunohistochemistry
In Situ Nick-End Labeling
Interleukin-4 - genetics
Interleukin-4 - pharmacology
Life Sciences
liver transplantation
Receptors, Interleukin-4 - genetics
Reverse Transcriptase Polymerase Chain Reaction
RNA, Messenger - genetics
STAT6 Transcription Factor - antagonists & inhibitors
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Summary:IL-4 is overexpressed in liver grafts during severe recurrent hepatitis C and rejection. Hepatocyte apoptosis is involved in both these phenomena. We therefore examined the proapoptotic effect of IL-4 on HepG2 cells and human hepatocytes in vitro, together with the underlying mechanisms. We first measured IL-4 receptor expression, STAT6 activation by IL-4, and STAT6 inhibition by an anti-IL-4 antibody or by STAT6 siRNA transfection. We then focused on the pathways involved in IL-4-mediated apoptosis and the role of STAT6 activation in apoptosis initiation. The IL-4 receptor was expressed on both cell types, and STAT6 was activated by IL-4. Both anti-IL-4 and STAT-6 siRNA inhibited this activation. IL-4 induced apoptosis of both HepG2 cells (P=0.008 vs. untreated control) and human hepatocytes (P
ISSN:0892-6638
1530-6860
DOI:10.1096/fj.06-6319com