TY - JOUR AU - A Iolascon, AU - S Volinia, AU - A Borriello, AU - L Giordani, AU - A Moretti, AU - V Servedio, AU - N Maiorano, AU - V Cucciolla, AU - V Criniti, AU - P Gasparini, AU - S Indaco, AU - F Della Ragione, PY - 2004/09/01 Y2 - 2024/03/28 TI - Genes transcriptionally modulated by interferon alpha2a correlate with the cytokine activity JF - Haematologica JA - haematol VL - 89 IS - 9 SE - Comparative Studies DO - 10.3324/%x UR - https://haematologica.org/article/view/3215 SP - 1046-1053 AB - 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 Sjogren'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. ER -