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

Milton W. Taylor, William M. Grosse, Joel E. Schaley, Corneliu Sanda, Xiaoning Wu, Shih Chang Chien, Fred Smith, Thomas G. Wu, Matthew Stephens, Mary W. Ferris, Jeanette N. McClintick, Ronald E. Jerome, Howard J. Edenberg

Research output: Contribution to journalArticle

73 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)107-118
Number of pages12
JournalJournal of Interferon and Cytokine Research
Volume24
Issue number2
DOIs
StatePublished - Feb 1 2004

ASJC Scopus subject areas

  • Immunology
  • Cell Biology
  • Virology

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    Taylor, M. W., Grosse, W. M., Schaley, J. E., Sanda, C., Wu, X., Chien, S. C., Smith, F., Wu, T. G., Stephens, M., Ferris, M. W., McClintick, J. N., Jerome, R. E., & Edenberg, H. J. (2004). Global Effect of PEG-IFN-α and Ribavirin on Gene Expression in PBMC in Vitro. Journal of Interferon and Cytokine Research, 24(2), 107-118. https://doi.org/10.1089/107999004322813354