Global Effect of PEG-IFN- α and Ribavirin on Gene Expression in PBMC In Vitro

Authors:
  • WGWilliam M. Grosse
    William M. Grosse
  • JSJoel E. Schaley
    Joel E. Schaley
  • CSCorneliu Sanda
    Corneliu Sanda
  • XWXiaoning Wu
    Xiaoning Wu
  • SCShih-Chang Chien
    Shih-Chang Chien
  • FSFred Smith
    Fred Smith
  • TWThomas G. Wu
    Thomas G. Wu
  • MSMatthew Stephens
    Matthew Stephens
  • MFMary W. Ferris
    Mary W. Ferris
  • JMJeanette N. McClintick
    Jeanette N. McClintick
  • RJRonald E. Jerome
    Ronald E. Jerome
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Abstract
Using oligonucleotide microarrays, we have examined the expression of 22,000 genes in peripheral blood cells treated with pegylated interferon-α2b (PEG-IFN-α) and ribavirin. Treatment with ribavirin had very little effect on gene expression, whereas treatment with PEG-IFN-α had a dramatic effect, modulating the expression of approximately 1000 genes (at p < 0.001). In addition to genes previously reported to be induced by type I or type II IFNs, many novel genes were found to be upregulated, including transcription factors, such as ATF3, ATF4, properdin, a key regulator of the complement pathway, a homeobox gene (HESX1), and an RNA editing enzyme (apobec3). Chemokines CXCL10 and CXCL11 were upregulated, whereas CXCL5 was downregulated. Cytokines interleukin-15 (IL-15) and IL-18 were also significantly induced, whereas IL-1α and IL-1β were downregulated. Most other interleukins were not affected. The results of the microarrays were confirmed by kinetic real-time PCR. These data indicate that IFN treatment causes upregulation of genes associated with the stress response, apoptosis, and signaling, and an equal number of genes are downregulated, including those associated with protein synthesis, specific cytokines and chemokines and other biosynthetic functions.

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