Secombes CJ. Interferon type I and type II responses in an Atlantic salmon (Salmo salar) SHK-1 cell line by the salmon TRAITS/SGP microarray. Physiol Genomics 32: [33][34][35][36][37][38][39][40][41][42][43][44] 2007. First published September 5, 2007; doi:10.1152/physiolgenomics.00064.2007 RNA was hybridized to an Atlantic salmon cDNA microarray (salmon 17K feature TRAITS/SGP array) in order to assess differential gene expression in response to IFN exposure. For IFN I and II, 47 and 72 genes were stimulated, respectively; most genes were stimulated by a single IFN type, but some were affected by both IFNs, indicating coregulation of the IFN response in fish. Real-time PCR analysis was employed to confirm the microarray results for selected differentially expressed genes in both a cell line and primary leukocyte cultures. transcriptome; immune; fish INTERFERONS (IFNs) are cytokines that have key roles in the regulation of both innate and adaptive immune responses. They exhibit a diverse range of activities including antiviral, antitumor, and immunomodulatory roles (4). There are three types of IFN known in mammals (I-III); however, to date only types I and II have been identified in fish. Type I consists of a large number of related proteins including the ␣-and -IFNs, which function principally in the antiviral response (55). Type II IFN is a single protein (IFN-␥) that originally was described for its macrophage-activating activity (59). The two families of IFN molecules are not structurally related but share similarities in their receptors and mechanisms of gene activation (41, 55). Type I and II IFNs produce their effect via different heterodimer cell surface receptors. Once IFN is bound to the receptor, signal transduction leads to activation of IFN-responsive genes via conserved signal transduction pathways leading to change of function of the cell (53). It is estimated in mammals that up to 200 or more genes may be affected by IFN stimulation (13). IFN-␥ signal transduction is primarily via the Janus-activated kinase (JAK)-signal transducer and activator of transcription (STAT) pathway. Here JAK1 associates with JAK2 on stimulation and causes the phosphorylation of STAT1. Two STAT1 molecules dimerize to form a homodimer, which then binds to specific consensus sequences in the promoter of IFN-␥-responsive genes at specific ␥-IFN activation site (GAS) elements, resulting in initiation of transcription. Type I IFN molecules follow a similar pathway, but there are two different kinases that are associated with the receptor. In this case JAK1 and tyrosine kinase 2 (TYK2) are activated and phosphorylate both STAT1 and STAT2, which form a heterodimer that in combination with interferon regulatory factor 9 forms a trimer that binds to interferon-stimulated response elements (IRSE) and subsequently induces transcription (reviewed in Refs. 41, 55). In mammals IFN type I can stimulate genes via both IRSE and GAS elements in the promoter, whereas IFN-␥ does not usually act via IRSE (41, 55), although many IFN-respon...