Differential transcriptional responses to interferon-alpha and interferon-gamma in primary human hepatocytes.
Interferon (IFN) plays a central role in the innate and adaptive antiviral immune responses. While IFN-alpha is currently approved for treating chronic hepatitis B and hepatitis C, in limited studies, IFN-gamma has not been shown to be effective for chronic hepatitis B or C. To identify the potential mechanism underlying the differential antiviral effects of IFN-alpha and IFN-gamma, we used cDNA microarray to profile the global transcriptional response to IFN-alpha and IFN-gamma in primary human hepatocytes, the target cell population of hepatitis viruses. Our results reveal distinct patterns of gene expression induced by these 2 cytokines. Overall, IFN-alpha induces more genes than IFN-gamma at the transcriptional level. Distinct sets of genes were induced by IFN-alpha and IFN-gamma with limited overlaps. IFN-alpha induces gene transcription at an early time point (6 h) but not at a later time point (18 h), while the effects of IFN-gamma are more prominent at 18 h than at 6 h, suggesting a delayed transcriptional response to IFN-gamma in the hepatocytes. These findings indicate differential actions of IFN-alpha and IFN-gamma in the context of therapeutic intervention for chronic viral infections in the liver.
He
Xiao-Song
XS
Department of Medicine, Stanford University School of Medicine , Stanford, California, USA.
Nanda
Santosh
S
Ji
Xuhuai
X
Calderon-Rodriguez
Gloria M
GM
Greenberg
Harry B
HB
Liang
T Jake
TJ
D018929:Cell Culture Techniques; D002478:Cells, Cultured; D020869:Gene Expression Profiling; D006509:Hepatitis B / Q000276:immunology / Q000628:therapy; D006526:Hepatitis C / Q000276:immunology / Q000628:therapy; D022781:Hepatocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology* / Q000627:therapeutic use; D007371:Interferon-gamma / Q000494:pharmacology* / Q000627:therapeutic use; D020411:Oligonucleotide Array Sequence Analysis
D016898:Interferon-alpha; D007371:Interferon-gamma