Genes transcriptionally modulated by interferon alpha2a correlate with the cytokine activity.

Abstract

BACKGROUND AND OBJECTIVES:

Interferon alpha2a (IFNalpha2a) mediates important antiviral, antiproliferative and immunomodulatory responses and is employed in the treatment of human diseases, including chronic myelogenous leukemia. Here, we report the IFNalpha2a-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 IFNalpha2a 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, IFNalpha2a 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 IFNalpha2a-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 IFNalpha2a could be related to the development of autoimmune syndromes observed during IFNalpha2a treatment. A number of genes transcriptionally regulated by the cytokine have been identified for the first time; these might represent additional effectors of IFNalpha2a activity.

• Authors: 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
• Journal: Haematologica (Haematologica) Vol. 89 Issue 9 Pg. 1046-53 (Sep 2004) ISSN: 1592-8721 [Electronic] Italy
• PMID: 15377465 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Apoptosis Regulatory Proteins
• Cytokines
• Interferon alpha-2
• Interferon-Stimulated Gene Factor 3, gamma Subunit
• Interferon-alpha
• MAL protein, human
• Membrane Transport Proteins
• Myelin Proteins
• Myelin and Lymphocyte-Associated Proteolipid Proteins
• Neoplasm Proteins
• Protein Synthesis Inhibitors
• Proteolipids
• Recombinant Proteins
• Ribonucleoproteins
• SS-A antigen
• STAT1 Transcription Factor
• STAT1 protein, human
• STAT2 Transcription Factor
• STAT2 protein, human
• Cycloheximide

Topics

• Apoptosis Regulatory Proteins (biosynthesis, genetics)
• Base Sequence
• Carcinoma, Hepatocellular (pathology)
• Cell Line, Tumor (drug effects, metabolism)
• Cycloheximide (pharmacology)
• Cytokines (biosynthesis, genetics)
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Interferon alpha-2
• Interferon-Stimulated Gene Factor 3, gamma Subunit (biosynthesis, genetics)
• Interferon-alpha (pharmacology)
• K562 Cells (drug effects, metabolism)
• Liver Neoplasms (pathology)
• Membrane Transport Proteins (biosynthesis, genetics)
• Molecular Sequence Data
• Myelin Proteins (biosynthesis, genetics)
• Myelin and Lymphocyte-Associated Proteolipid Proteins
• Neoplasm Proteins (biosynthesis, genetics)
• Oligonucleotide Array Sequence Analysis
• Promoter Regions, Genetic
• Protein Synthesis Inhibitors (pharmacology)
• Proteolipids (biosynthesis, genetics)
• Recombinant Proteins
• Rhabdomyosarcoma (pathology)
• Ribonucleoproteins (biosynthesis, genetics)
• STAT1 Transcription Factor (biosynthesis, genetics)
• STAT2 Transcription Factor (biosynthesis, genetics)
• Transcription, Genetic (drug effects)