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


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.


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.
Iolascon
Achille
A
Medical Genetics University Federico II, Naples, Italy.
Volinia
Stefano
S
Borriello
Adriana
A
Giordani
Lucia
L
Moretti
Arcangela
A
Servedio
Veronica
V
Maiorano
Nunzia
N
Cucciolla
Valeria
V
Criniti
Vittoria
V
Gasparini
Paolo
P
Indaco
Stefania
S
Della Ragione
Fulvio
F
D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis / Q000235:genetics; D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000473:pathology; D045744:Cell Line, Tumor / Q000187:drug effects / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D000077190:Interferon alpha-2; D050834:Interferon-Stimulated Gene Factor 3, gamma Subunit / Q000096:biosynthesis / Q000235:genetics; D016898:Interferon-alpha / Q000494:pharmacology*; D020014:K562 Cells / Q000187:drug effects / Q000378:metabolism; D008113:Liver Neoplasms / Q000473:pathology; D026901:Membrane Transport Proteins / Q000096:biosynthesis / Q000235:genetics; D008969:Molecular Sequence Data; D009185:Myelin Proteins / Q000096:biosynthesis / Q000235:genetics; D062806:Myelin and Lymphocyte-Associated Proteolipid Proteins; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011510:Proteolipids / Q000096:biosynthesis / Q000235:genetics; D011994:Recombinant Proteins; D012208:Rhabdomyosarcoma / Q000473:pathology; D012261:Ribonucleoproteins / Q000096:biosynthesis / Q000235:genetics; D050794:STAT1 Transcription Factor / Q000096:biosynthesis / Q000235:genetics; D050795:STAT2 Transcription Factor / Q000096:biosynthesis / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects*; D000099207:SS-A Antigen
D051017:Apoptosis Regulatory Proteins; D003513:Cycloheximide; D016207:Cytokines; D000077190:Interferon alpha-2; D050834:Interferon-Stimulated Gene Factor 3, gamma Subunit; D016898:Interferon-alpha; D026901:Membrane Transport Proteins; D009185:Myelin Proteins; D062806:Myelin and Lymphocyte-Associated Proteolipid Proteins; D009363:Neoplasm Proteins; D011500:Protein Synthesis Inhibitors; D011510:Proteolipids; D011994:Recombinant Proteins; D012261:Ribonucleoproteins; D050794:STAT1 Transcription Factor; D050795:STAT2 Transcription Factor; D000099207:SS-A Antigen; C569026:MAL protein, human; C494079:STAT1 protein, human; C494084:STAT2 protein, human