Global effect of PEG-IFN-alpha and ribavirin on gene expression in PBMC in vitro.
Using oligonucleotide microarrays, we have examined the expression of 22,000 genes in peripheral blood cells treated with pegylated interferon-alpha2b (PEG-IFN-alpha) and ribavirin. Treatment with ribavirin had very little effect on gene expression, whereas treatment with PEG-IFN-alpha 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-1alpha and IL-1beta 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.
Taylor
Milton W
MW
Department of Biology, Indiana University, Bloomington, IN 47405, USA. taylor@indiana.edu
Grosse
William M
WM
Schaley
Joel E
JE
Sanda
Corneliu
C
Wu
Xiaoning
X
Chien
Shih-Chang
SC
Smith
Fred
F
Wu
Thomas G
TG
Stephens
Matthew
M
Ferris
Mary W
MW
McClintick
Jeanette N
JN
Jerome
Ronald E
RE
Edenberg
Howard J
HJ
D002478:Cells, Cultured; D018925:Chemokines / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology*; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology*; D020411:Oligonucleotide Array Sequence Analysis; D011092:Polyethylene Glycols; D012333:RNA, Messenger / Q000235:genetics; D011994:Recombinant Proteins; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012254:Ribavirin / Q000494:pharmacology*
D018925:Chemokines; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012333:RNA, Messenger; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C417083:peginterferon alfa-2b; C100416:peginterferon alfa-2a