Disease relevance of ISG15

• Ovine UCRP was also detected in uterine flushings from Days 15 and 17 of pregnancy and immunoprecipitated from Day 17 pregnant endometrial explant-conditioned medium [1].

High impact information on ISG15

• Immunohistochemistry revealed that ISG15 was localized throughout the endometrium on d 18-23, with heaviest staining in the sublumenal stratum compactum and the glandular epithelium throughout the stratum spongiosum [2].
• Using transmission electron microscopy and immunogold labeling, ISG15 was specifically localized to organelles and compartments of endometrial epithelial cells and stromal cells: nucleus, perinuclear space, cytosol, mitochondria, rough endoplasmic reticulum, and cell membrane [2].
• The interferon-stimulated gene ISG15, a ubiquitin homolog, becomes conjugated to and regulates uterine proteins in response to conceptus-derived interferon-tau on d 18 of pregnancy [2].
• This specific localization in epithelial and stromal cells led to the conclusion that ISG15 has diverse intracellular functions [2].
• By d 45 and 50, ISG15 was lightly stained only in the stratum compactum immediately beneath the lumenal epithelium [2].

Biological context of ISG15

• ISG15 and its conjugates were not detected on d 50 of pregnancy or during the estrous cycle [2].
• It was hypothesized that pregnancy induces blood cell ISG15 gene expression and that low blood ISG15 mRNA levels provide an indication of non-pregnant cows on day 18 [3].
• It is concluded that detection of low blood ISG15 mRNA levels during serial collection from days 17 to 25 serves as an accurate indicator of cows that are not pregnant, thus allowing re-synchronization and insemination [3].
• The present experiments were designed to determine whether detection (Western blot) of cytosolic UCRP and release of GCP-2 could be used to examine IFN-tau signal transduction in cultured endometrial explants and primary epithelial cells [4].

Anatomical context of ISG15

• Localization of ISG15 and conjugated proteins in bovine endometrium using immunohistochemistry and electron microscopy [2].
• The average pregnancy rate was 43% based on blood cell ISG15 mRNA [3].
• Northern blots using radiolabeled UCRP cDNA revealed a single UCRP transcript of approximately 700 b that was present (P < 0.05) in endometrial cells cultured with 25 nM rboIFN-tau [5].
• Ubiquitin cross-reactive protein is released by the bovine uterus in response to interferon during early pregnancy [6].
• All concentrations of rboIFN-alpha (25, 50, 100 nM) induced UCRP, but only the highest concentration induced GCP-2 in cultured primary epithelial cells [4].

Associations of ISG15 with chemical compounds

• Low blood ISG15 mRNA and progesterone levels are predictive of non-pregnant dairy cows [3].

Regulatory relationships of ISG15

• We conclude that transcription of the UCRP gene is transient during early pregnancy and regulated by IFN-tau [5].

Other interactions of ISG15

• The UCRP mRNA was not detected in endometrium on days 15, 17, 18 or 19 of the estrous cycle (n = 4 cows on each day) or in spleen, kidney, liver, corpus luteum or muscle [5].
• The objectives of the present experiments were to determine whether UCRP became conjugated to endometrial cytosolic proteins during early pregnancy and in response to recombinant bovine (rbo) IFN-tau [7].
• Steady-state levels of mRNA for Mx1, Mx2, beta2-microglobulin, ISG-15, IFN regulatory factor-1, and IFN regulatory factor-2 were quantified [8].

Analytical, diagnostic and therapeutic context of ISG15

• Intracellular ISG15 and its conjugates were present on d 17 of pregnancy, peaked to highest levels from d 18 to 23 and then declined to low but detectable levels by d 45 (P < 0.05) based on Western blotting [2].
• ISG15 mRNA levels were determined using real-time PCR [3].

References