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 (IFN tau), a type I IFN produced by sheep conceptus trophect oderm, is the signal for maternal recognition of pregnancy. Although it is clear that IFN tau suppresses transcription of the estrogen receptor a and oxytocin receptor genes and induces expression of various IFN-stimulated ge nes within the endometrial epithelium, little is known of the signal transd uction pathway activated by the hormone. This study determined the effects of IFN tau on signal transducer and activator of transcription (STAT) activ ation, expression, DNA binding, and transcriptional activation using an ovi ne endometrial epithelial cell line. IFN tau induced persistent tyrosine ph osphorylation and nuclear translocation of STAT1 and -2 (10 min to 48 h), b ut transient phosphorylation and nuclear translocation of STATE, -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 for med and bound an IFN-stimulated response element (ISRE) and gamma -activate d sequence (GAS) element, respectively. IFN tau increased transcription of GAS-driven promoters at 3 h, but suppressed their activity at 24 h. In cont rast, 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 differ ential effects on ISRE- and GAS-driven gene transcription.