The Interferon Stimulated Genes (ISG) 17 and Mx have different temporal and spatial expression in the ovine uterus suggesting more complex regulation of the Mx gene

Abstract

Interferon stimulated gene 17 (ISG17) and Mx are up-regulated in the ruminant uterus in response to interferon-tau (IFN ) during early pregnancy. Recent evidence strongly indicates that expression of ISGs occur only in stroma (ST) and glandular epithelium (GE) during this time as a result of transcriptional repression by interferon regulatory factor two (IRF-2) expression in the LE. The present report tested this hypothesis by examining mRNA and protein expression of ISG17 and Mx in serial uterine cross-sections obtained from cyclic and early pregnant ewes. In situ and immunocytochemical analysis revealed that ISG17 mRNA and protein were low to undetectable, whereas Mx mRNA was expressed in the lumenal (LE) and superficial GE at all days of the estrous cycle examined. Both ISG17 and Mx mRNA increased in the stratum compactum ST between Days 11 and 13, and expression extended into the deep GE and stratum spongiosum ST on Days 15 through 17 in pregnant ewes. Interestingly the Mx gene continued to be strongly expressed in LE and superficial GE through Day 17 of pregnancy, whereas ISG17 remained low to undetectable in these cells. Collectively, this study highlights the complexity of the uterine environment by unequivocally illustrating differential temporal and spatial expression of the IFN-responsive genes ISG17 and Mx.

Pregnancy and Interferon Tau Regulate Major Histocompatibility Complex Class I and β2-Microglobulin Expression in the Ovine Uterus1

“…However, expression was not detected thereafter or in progesterone-treated Day 17 cyclic ewes infused with control proteins from Days 11 to 16 from study 2. The expression of several other ISGs, including ISG17, OAS, and IRF-1, has been observed at low levels in the endometrial LE and sGE [28,29,33,35]. A possible explanation is that positive-and negative-acting transcription factors simultaneously regulate expression of these genes.…”

“…The IFN induces or increases expression of many IFN-stimulated genes (ISGs) in a celltype specific manner in the uterine endometrium. These ISGs include ␤2MG [23], Stat1 and Stat2 [24][25][26][27][28], IRF-1 [24,25,27,28], ISG17 [25,[29][30][31], Mx protein [32,33], and 2Ј,5Ј-oligoadenylate synthetase (OAS) [34,35]. The IFN regulates gene transcription through an intracellular signal transduction system involving Stats and IRFs [25][26][27][28].…”

Expression of Cyclooxygenase-2 and Granulocyte-Macrophage Colony-Stimulating Factor in the Endometrial Epithelium of the Cow Is Up-Regulated During Early Pregnancy and in Response to Intrauterine Infusions of Interferon-τ1

“…Another group of 18 heifers was observed for at least one natural estrous cycle before breeding by artificial insemination. Reproductive tracts were collected on Days 7,16,18,21,24, and 30 of gestation (n ϭ 3 per day). These days were chosen based on the IFN-timeframe (d16P, d18P, d21P, and d24P), with d7P and d30P respectively serving as controls before and after the major output of IFN- [8][9][10].…”

“…In the endometrium, IFN-has been shown to stimulate granulocyte chemotactic protein-2 [13] and monocyte chemotactic protein-1 and -2 [14], IFN-␥-inducible protein 10 kDa [15], IFN-stimulated gene product 17 [16], 2Ј5Ј-oligoadenylate-synthetase [17], 1-8U and Leu-13 [18], major histocompatibility complex class I and beta-2-microglobulin [19], Mx protein [20,21], signal transducer and activator of transcription 1 and 2, interferon regulatory factor (IRF) 1 and IRF9 [22]. In the ovine uterus, the receptor for type I interferons is predominantly expressed in the luminal epithelium (LE) and shallow glands (SG) but also in the caruncular stroma [23].…”

Bovine Herpesvirus 1 protein bICP0 represses the transcription of bISG15 in fetal bovine lung cells

“…As shown in Fig. 3, bIRF-3 and enzymes involved in ISG15 modification are interferon inducible [4,5,9,12,19] . ISG15 and its modified form play important roles in innate immunity and antiviral response to infection, so it is reasonable that BHV-1 evolved via some mechanism to inhibit bISG15 and its modification system.…”