Interferon-tau (IFN tau) regulation of IFN-stimulated gene expression in cell lines lacking specific IFN-signaling components

Interferon-tau (IFN tau) is a unique type I IFN secreted by the ruminant co nceptus that acts in a paracrine manner on the endometrial epithelium to si gnal pregnancy recognition. In the ovine endometrium, IFN tau suppresses es trogen receptor a and oxytocin receptor gene expression, but increases or i nduces expression of IFN-simulated genes (ISGs), including signal transduce r and activator of transcription-1 (STAT1), STAT2, ISG factor-3 gamma (ISGF 3 gamma)/p48/IFN regulatory factor-9, and 2 ' ,5 ' -oligoadenylate syntheta se (OAS). Human fibroblast cell lines lacking specific IFN signaling compon ents were employed to determine the roles of STAT1, STATE, and ISGF3 gamma in the effects of IFN tau on ISG protein expression. Results indicated that STAT1 alpha or STAT1 beta is required for IFN tau effects on STAT2, ISGF3 gamma, and OAS (40/46, 69/71, and 100 kDa). STAT2 is required for effects o n STAT1, ISGF3 gamma, and all OAS forms. ISGF3 gamma is required for effect s of IFN tau on STAT2 and 40/46- and 69/71-kDa OAS and plays a role in the effects of IFN tau on 100-kDa OAS and STAT1. Mutation of Tyr(701), but not Ser(727), Of STAT1 abolished the effects of IFN tau on ISG expression; Muta tion of the SH2 domain of STAT1 abolished the effects of IFN tau on all ISG s and reduced increases in 100-kDa GAS. These data illustrate the importanc e of transcription factors composed of STAT1, STAT2, and ISGF3 gamma in the signaling pathway mediating the effects of IFN tau on ISG expression.