title: Genes transcriptionally modulated by interferon alpha2a correlate with the cytokine activity.
abstract: 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.
authors.affiliation: Medical Genetics University Federico II, Naples, Italy.
authors.forename: Achille
authors.initials: A
authors.lastname: Iolascon
authors.forename: Stefano
authors.initials: S
authors.lastname: Volinia
authors.forename: Adriana
authors.initials: A
authors.lastname: Borriello
authors.forename: Lucia
authors.initials: L
authors.lastname: Giordani
authors.forename: Arcangela
authors.initials: A
authors.lastname: Moretti
authors.forename: Veronica
authors.initials: V
authors.lastname: Servedio
authors.forename: Nunzia
authors.initials: N
authors.lastname: Maiorano
authors.forename: Valeria
authors.initials: V
authors.lastname: Cucciolla
authors.forename: Vittoria
authors.initials: V
authors.lastname: Criniti
authors.forename: Paolo
authors.initials: P
authors.lastname: Gasparini
authors.forename: Stefania
authors.initials: S
authors.lastname: Indaco
authors.forename: Fulvio
authors.initials: F
authors.lastname: Della Ragione
mesh_terms: 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
chemical_list: 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