Identification of genes differentially regulated by interferon alpha, beta, or gamma using oligonucleotide arrays

The pleiotropic activities of interferons (IFNs) are mediated primarily thr ough the transcriptional regulation of many downstream effector genes. The mRNA profiles from IFN-alpha, -beta, or -gamma treatments of the human fibr osarcoma cell line, HT1080, were determined by using oligonucleotide arrays with probe sets corresponding to more than 6,800 human genes. Among these were transcripts for known IFN-stimulated genes (ISGs), the expression of w hich were consistent with previous studies in which the particular ISG was characterized as responsive to either Type I (alpha, beta) or Type II (gamm a) IFNs, or both. Importantly, many novel IFN-stimulated genes were identif ied that were diverse in their known biological functions. For instance, se veral novel ISGs were identified that are implicated in apoptosis (includin g RAP46/Bag-1, phospholipid scramblase, and hypoxia inducible factor-1 alph a). Furthermore, several IFN-repressed genes also were identified. These re sults demonstrate the usefulness of oligonucleotide arrays in monitoring ma mmalian gene expression on a broad and unprecedented scale. In particular, these findings provide insights into the basic mechanisms of IFN actions an d ultimately may contribute to better therapeutic uses for IFNs.