This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Stewart, M. D. Articles by Spencer, T. E. Search for Related Content PubMed PubMed Citation Articles by Stewart, M. D. Articles by Spencer, T. E.

Interferon- (IFN) Regulation of IFN-Stimulated Gene Expression in Cell Lines Lacking Specific IFN-Signaling Components¹

Center for Animal Biotechnology and Genomics, Department of Animal Science, Texas A&M University, College Station, Texas 77843-2471

Address all correspondence and requests for reprints to: Thomas E. Spencer, Center for Animal Biotechnology and Genomics, 442 Kleberg Center, 2471 TAMU, Texas A&M University, College Station, Texas 77843-2471. E-mail: tspencer{at}ansc.tamu.edu

Interferon- (IFN) is a unique type I IFN secreted by the ruminant conceptus that acts in a paracrine manner on the endometrial epithelium to signal pregnancy recognition. In the ovine endometrium, IFN suppresses estrogen receptor and oxytocin receptor gene expression, but increases or induces expression of IFN-simulated genes (ISGs), including signal transducer and activator of transcription-1 (STAT1), STAT2, ISG factor-3 (ISGF3)/p48/IFN regulatory factor-9, and 2',5'-oligoadenylate synthetase (OAS). Human fibroblast cell lines lacking specific IFN signaling components were employed to determine the roles of STAT1, STAT2, and ISGF3 in the effects of IFN on ISG protein expression. Results indicated that STAT1 or STAT1ß is required for IFN effects on STAT2, ISGF3, and OAS (40/46, 69/71, and 100 kDa). STAT2 is required for effects on STAT1, ISGF3, and all OAS forms. ISGF3 is required for effects of IFN on STAT2 and 40/46- and 69/71-kDa OAS and plays a role in the effects of IFN on 100-kDa OAS and STAT1. Mutation of Tyr⁷⁰¹, but not Ser⁷²⁷, of STAT1 abolished the effects of IFN on ISG expression. Mutation of the SH2 domain of STAT1 abolished the effects of IFN on all ISGs and reduced increases in 100-kDa OAS. These data illustrate the importance of transcription factors composed of STAT1, STAT2, and ISGF3 in the signaling pathway mediating the effects of IFN on ISG expression.