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Endocrinology Vol. 142, No. 1 98-107
Copyright © 2001 by The Endocrine Society

ARTICLES

Interferon-{tau} Activates Multiple Signal Transducer and Activator of Transcription Proteins and Has Complex Effects on Interferon-Responsive Gene Transcription in Ovine Endometrial Epithelial Cells1

David M. Stewart, Greg A. Johnson, Carrie A. Vyhlidal, Robert C. Burghardt, Stephen H. Safe, Li-Yuan Yu-Lee, Fuller W. Bazer and Thomas E. Spencer

Center for Animal Biotechnology and Genomics, Department of Animal Science, Texas A&M University (D.S., G.A.J., F.W.B., T.E.S.), and Departments of Veterinary Physiology and Pharmacology (C.A.V., S.H.S.) and Veterinary Anatomy and Public Health (R.C.B.), Texas A&M University College of Veterinary Medicine, College Station, Texas 77843; and Departments of Medicine, Molecular and Cellular Biology and Immunology, Baylor College of Medicine (L.-Y.Y.-L.), Houston, Texas 77030

Address all correspondence and requests for reprints to: Dr. 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-{tau} (IFN{tau}), a type I IFN produced by sheep conceptus trophectoderm, is the signal for maternal recognition of pregnancy. Although it is clear that IFN{tau} suppresses transcription of the estrogen receptor {alpha} and oxytocin receptor genes and induces expression of various IFN-stimulated genes within the endometrial epithelium, little is known of the signal transduction pathway activated by the hormone. This study determined the effects of IFN{tau} on signal transducer and activator of transcription (STAT) activation, expression, DNA binding, and transcriptional activation using an ovine endometrial epithelial cell line. IFN{tau} induced persistent tyrosine phosphorylation and nuclear translocation of STAT1 and -2 (10 min to 48 h), but transient phosphorylation and nuclear translocation of STAT3, -5a/b, and -6 (10 to <60 min). IFN{tau} increased expression of STAT1 and -2, but not STAT3, -5a/b, and -6. IFN-stimulated gene factor-3 and STAT1 homodimers formed and bound an IFN-stimulated response element (ISRE) and {gamma}-activated sequence (GAS) element, respectively. IFN{tau} increased transcription of GAS-driven promoters at 3 h, but suppressed their activity at 24 h. In contrast, the activity of an ISRE-driven promoter was increased at 3 and 24 h. These results indicate that IFN{tau} activates multiple STATs and has differential effects on ISRE- and GAS-driven gene transcription.




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