Genes transcriptionally modulated by interferon α2a correlate with the cytokine activity

Achille Iolascon, Stefano Volinia, Adriana Borriello, Lucia Giordani, Arcangela Moretti, Veronica Servedio, Nunzia Maiorano, Valeria Cucciolla, Vittoria Criniti, Paolo Gasparini, Stefania Indaco, Fulvio Della Ragione

Research output: Contribution to journalArticlepeer-review

Abstract

Background and Objectives. Interferon α2a (IFNα2a) mediates important antiviral, antiproliferative and immunomodulatory responses and is employed in the treatment of human diseases, including chronic myelogenous leukemia. Here, we report the IFNα2a-dependent expression profiles of three malignant cell lines derived from liver, lymphocytes and muscle. Design and Methods. The experiments were performed in the presence of cycloheximide, thus our results exclusively reflect direct transcriptional modulation. The short exposure time i.e. 5 hours evidences only the early events, excluding the effects of complex phenotypic changes on the expression. Results. Our findings indicate that IFNα2a rapidly up-regulates the expression of STAT1, STAT2 and ISGF3G genes. This activity should result in the amplification of the cellular response to the cytokine. Moreover, IFNα2a directly modulates the expression of: (i) important transcriptional factors, e.g. IRF1 and IRF7 which control pivotal cellular events, and (ii) enzymes involved in the IFNα2a-dependent antiviral and apoptotic response. Interestingly, we showed that the cytokine induces transcriptional expression of Sjögren's syndrome antigen A1, a protein involved in several autoimmune diseases. Interpretation and Conclusions. The observed changes induced by IFNα2a could be related to the development of autoimmune syndromes observed during IFNα2a treatment. A number of genes transcriptionally regulated by the cytokine have been identified for the first time; these might represent additional effectors of IFNα2a activity.

Original languageEnglish
Pages (from-to)1046-1053
Number of pages8
JournalHaematologica
Volume89
Issue number9
Publication statusPublished - Sep 2004

Keywords

  • Expression profile
  • HepG2
  • Interferon α2a
  • K562; RH-30

ASJC Scopus subject areas

  • Hematology

Fingerprint Dive into the research topics of 'Genes transcriptionally modulated by interferon α2a correlate with the cytokine activity'. Together they form a unique fingerprint.

Cite this