Interferon-tau activates multiple signal transducer and activator of transcription proteins and has complex effects on interferon-responsive gene transcription in ovine endometrial epithelial cells.
Interferon-tau (IFNtau), a type I IFN produced by sheep conceptus trophectoderm, is the signal for maternal recognition of pregnancy. Although it is clear that IFNtau 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 IFNtau on signal transducer and activator of transcription (STAT) activation, expression, DNA binding, and transcriptional activation using an ovine endometrial epithelial cell line. IFNtau 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). IFNtau 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. IFNtau 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 IFNtau activates multiple STATs and has differential effects on ISRE- and GAS-driven gene transcription.
Stewart
M D
MD
Center for Animal Biotechnology and Genomics, Department of Animal Science, Texas A&M University, University College of Veterinary Medicine, College Station, Texas 77843, USA.
Stewart
D M
DM
Johnson
G A
GA
Vyhlidal
C A
CA
Burghardt
R C
RC
Safe
S H
SH
Yu-Lee
L Y
LY
Bazer
F W
FW
Spencer
T E
TE
D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D004717:Endometrium / Q000166:cytology / Q000502:physiology*; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology*; D005260:Female; D007370:Interferon Type I / Q000494:pharmacology* / Q000502:physiology; D050832:Interferon-Stimulated Gene Factor 3; D008156:Luciferases; D010766:Phosphorylation; D011257:Pregnancy Proteins / Q000494:pharmacology* / Q000502:physiology; D011401:Promoter Regions, Genetic; D021381:Protein Transport; D011993:Recombinant Fusion Proteins / Q000032:analysis; D050794:STAT1 Transcription Factor; D050795:STAT2 Transcription Factor; D012756:Sheep; D015398:Signal Transduction; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects / Q000502:physiology*; D014162:Transfection
D004268:DNA-Binding Proteins; D007370:Interferon Type I; D050832:Interferon-Stimulated Gene Factor 3; D011257:Pregnancy Proteins; D011993:Recombinant Fusion Proteins; D050794:STAT1 Transcription Factor; D050795:STAT2 Transcription Factor; D015534:Trans-Activators; D014157:Transcription Factors; C020947:interferon tau; D008156:Luciferases