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T L Ott

Publications and source records attributed to T L Ott.

At least 37 records · Page 2Linked to original sources
PubMed1998

Structural responses of pulmonary intravascular macrophages in lentivirus-infected and/or recombinant ovine interferon-tau-treated lambs.

Ovine lentivirus (OvLV), a retrovirus, infects and disseminates to various tissue organs via monocytes. The differentiation of infected monocytes into macrophages is a prerequisite for viral replication, and the presence of infected macrophages in tissue organs induces chronic immunopathology such as lymphoid interstitial pneumonia. The pulmonary intravascular macrophage (PIM) is a recently identified mononuclear phagocyte in domestic animal species, including sheep. Recombinant ovine interferon-tau (roIFN-tau), a type I IFN originally named as the ovine trophoblast protein, has potent antiviral activity against OvLV and human immunodeficiency virus and prevents the development of OvLV-associated lung pathology. We investigated and compared the structural features of PIMs in OvLV-infected and/or roIFN-tau-treated 1-month-old lambs using transmission electron microscopy. The PIMs' numerical counts were performed in toluidine blue-stained sections of Epoxy-embedded lung tissues. A reduction in the number of PIMs was observed with OvLV infection and/or roIFN-tau treatment of lambs as compared to the control group (P < or = 0.05). The majority of the PIMs in OvLV-infected and/or roIFN-tau-treated groups were devoid of their surface coat. The PIMs of OvLV-infected lambs exhibited signs of biosynthetic activation such as expanded rough endoplasmic reticulum, prominent Golgi complexes, and accumulation of secretory vesicles. A few PIMs contained OvLV-like structures. In roIFN-tau-treated OvLV-infected lambs, the lymphocytes had ruffled plasma membranes and were in intimate contact with the PIMs, as is observed during cytotoxic cell-mediated killing of target cells. Most of the PIMs in roIFN-tau-treated OvLV-infected lambs appeared smaller in size. Ovine lentivirus and roIFN-tau, individually or in combination, alter the integrity of the surface coat of PIMs and cause their disappearance from the lungs. Ovine lentivirus infection induces morphological changes that correlate with cytotoxic cell behavior between lymphocytes and PIMs in roIFN-tau-treated or placebo-treated lambs. The loss of PIMs, probably infected with OvLV, either through direct killing by roIFN-tau or indirectly by roIFN-tau-activated cytotoxic T lymphocytes may represent different aspects of therapeutic actions of this cytokine.

Animals↗
PubMed1998

Maternal dietary protein deficiency decreases nitric oxide synthase and ornithine decarboxylase activities in placenta and endometrium of pigs during early gestation.

Little is known about the mechanism responsible for retarded placental and fetal growth induced by maternal dietary protein malnutrition. On the basis of the recent finding that nitric oxide (NO) and polyamines (products of L-arginine) play an important role in embryonic and placental development, the present study was designed to determine whether protein deficiency decreases placental and endometrial activities of NO synthase (NOS) and ornithine decarboxylase (ODC) (the first and key regulatory enzyme in polyamine synthesis). Primiparous gilts selected genetically for low or high plasma total cholesterol concentrations (low line and high line, respectively) were mated and then fed 1.8 kg/d of isocaloric diets containing 13% or 0.5% crude protein. At d 40 or 60 of gestation, they were hysterectomized, and placenta and endometrium were obtained for incubations, NOS and ODC assays, and measurements of free amino acids and polyamines. Maternal dietary protein restriction decreased arginine and ornithine concentrations, constitutive and inducible NOS activities and NO production, as well as ODC activity and polyamine concentrations in placenta and endometrium of both lines of gilts. Placental NO synthase activity and NO generation were lower in high line gilts than in low line gilts. ODC activities and polyamine concentrations in placenta and endometrium were decreased at d 60 compared with d 40 of gestation. These changes in placental and endometrial synthesis of NO and polyamines during early gestation may be a mechanism responsible for reduced placental and fetal growth in protein-deficient gilts and for altered conceptus development in high line gilts.

Amino Acids↗
PubMed1998

Expression of interferon regulatory factors one and two in the ovine endometrium: effects of pregnancy and ovine interferon tau.

Availàble evidence suggests that interferon tau (IFNtau), the signal for pregnancy recognition in ruminants, suppresses transcription of the estrogen receptor (ER) gene in the endometrial lumenal epithelium (LE) and superficial glandular epithelium (sGE) to prevent oxytocin receptor (OTR) expression and pulsatile release of luteolytic prostaglandin F2alpha. The IFN regulatory factors one (IRF-1) and two (IRF-2) are transcription factors induced by type I IFNs that activate and silence gene expression, respectively. The objectives of these studies were to determine effects of pregnancy and IFNtau on expression of immunoreactive IRF-1 and IRF-2 proteins in the ovine endometrium. In study one, IRF-1 and IRF-2 were not detected in the LE or sGE of cyclic ewes. In pregnant ewes, IRF-1 expression was detected transiently in the LE and sGE only on Days 11 and 13, and IRF-2 was detected in these same epithelia on Days 13, 15, 17, and 20. In study two, 36 ewes were fitted with uterine catheters on Day 5 of the estrous cycle, and one uterine horn was double-ligated at the base. Uterine horns of each ewe received twice-daily injections of either recombinant ovine IFNtau or control proteins beginning on Day 11 until hysterectomy at 1, 3, 6, 12, 24, 48, 72, 96, or 120 h after initial injection. The IRF-1 was detected transiently in the endometrial LE and sGE only at 12 and 24 h in the uterine horn receiving IFNtau but not in those tissues receiving control proteins. The IRF-2 was expressed in the LE and sGE at 24 h and thereafter in the IFNtau-treated, but not control uterine horns. In control uterine horns, ER and OTR were first detected in the LE at 48 h and 72 h, respectively, and remained abundant thereafter. In horns receiving IFNtau, ER and OTR expression was not detected in the endometrial LE and sGE. Results suggest that IFNtau acts directly on the LE and sGE during pregnancy to sequentially induce IRF-1 and then IRF-2 gene expression, which is correlated temporally with an absence of ER and OTR. The ovine ER gene may contain an IFNtau-responsive element(s) that binds negative-acting, IFNtau-inducible transcription factors, such as IRF-2, which silences transcription of the ER gene in the endometrial epithelium during maternal recognition of pregnancy.

Animals↗
PubMed1998

Effects of the estrous cycle and early pregnancy on uterine expression of Mx protein in sheep (Ovis aries).

Conceptuses of ruminant ungulates produce large amounts of a type I interferon, interferon-tau (IFNtau), which is the signal for maternal recognition of pregnancy. Induction of cellular Mx proteins is an important component of the response to type I interferon in the immune system, but Mx regulation and function have not been studied in the uterus. This study examined temporal and spatial alterations in ovine uterine Mx expression during the cycle and early pregnancy using immunohistochemistry, in situ hybridization, and Northern and slot-blot analysis. Sheep uterine endometrium expressed a single approximately 2.5-kilobase Mx mRNA transcript that was detectable at all stages of the estrous cycle and early pregnancy examined. In cyclic ewes, mRNA abundance in endometrium increased from Day 1 to peak levels at Day 13 and then declined to Day 15. In pregnant ewes, steady-state levels of Mx mRNA were first detected above the level in cyclic ewes at Day 13 postmating, were greater than 10-fold higher at Day 15, and remained elevated at Day 19. Expression of Mx mRNA in the myometrium did not change during the estrous cycle but increased approximately 23-fold between Days 11 and 15 of pregnancy. Immunohistochemical and in situ hybridization analysis revealed a similar temporal pattern of Mx expression. In cyclic ewes, Mx protein and mRNA were initially localized to the luminal epithelium at Days 1 and 3, increased from Days 5 to 13, especially in the shallow uterine glands, and then declined at Day 15. Pregnancy resulted in up-regulation of Mx expression in the luminal and glandular epithelium, stroma, and myometrium. Punctate Mx immunostaining and Mx mRNA concentrations were greatest when progesterone production was maximal during the estrous cycle and were strongly up-regulated by the conceptus across the entire uterine wall. It is suggested that a cascade of induction of Mx gene expression proceeds from the luminal epithelium to the outer longitudinal myometrium and that transcriptional activation of the promoter may involve both soluble cytokines (i.e., IFNtau) and steroid hormones (i.e., progesterone).

Animals↗
PubMed1997

Potent anti-feline immunodeficiency virus and anti-human immunodeficiency virus effect of IFN-tau.

Ovine IFN-tau is a newly described protein related to IFN-alpha that is responsible for maternal recognition of pregnancy in sheep. It has been shown to exhibit potent antiviral and antiproliferative activity. To determine its antiviral activity against feline immunodeficiency virus (FIV) and HIV, the activity of the RNA-dependent DNA polymerase, reverse transcriptase, was assayed in FIV- and HIV-infected feline and human PBL treated with IFN-tau. Significant dose-dependent inhibition of reverse transcriptase activity by IFN-tau was detected by day 6 of culture and was maintained through the peak of virus replication. In addition, production of the FIV core protein, p25, was blocked by IFN-tau. Both the amino- and carboxyl-terminal regions of IFN-tau, as identified by synthetic peptides, appear to be involved in its antiretroviral activity. Comparison of the anti-HIV activities of IFN-tau and recombinant human IFN-alpha2 (rHuIFN-alpha2) indicated that while rHuIFN-alpha2 was toxic to cells at 10,000 U/ml, IFN-tau antiretroviral activity was not associated with a decrease in either cell viability or immunologic reactivity. Thus, IFN-tau displayed potent anti-FIV and anti-HIV activity without the cytotoxicity associated with high concentrations of rHuIFN-alpha2.

Animals↗
PubMed1997

Effects of exogenous recombinant ovine interferon tau on circulating concentrations of progesterone, cortisol, luteinizing hormone, and antiviral activity; interestrous interval; rectal temperature; and uterine response to oxytocin in cyclic ewes.

Interferon tau (IFN tau) is the conceptus-produced antiluteolytic signal in ruminants. Three experiments examined the effects of s.c. administration of recombinant ovine (ro)IFN tau on interestrous interval (IEI), oxytocin (OT)-induced uterine prostaglandin F2alpha metabolite (PGFM) production, rectal temperature (RT), respiration rate (RR), and plasma concentrations of progesterone, cortisol, LH, and antiviral activity (AVA) in plasma and uterine flushings. In experiment I, 20 ewes were treated s.c. with either 0, 1, 2, or 4 mg/day roIFN tau (0.7 x 10(8) U/mg; 5 ewes/dosage) from Days 11 to 15 of the estrous cycle (estrus = Day 0) and were challenged with OT (30 IU) on Day 15. Jugular blood samples were collected at -10, 0, 10, 20, 30, 40, 50, and 60 min relative to the OT challenge and assayed for PGFM. Recombinant oIFN tau increased IEI (16.7, 18.7, and 22.6 +/- 0.6 days for 0, 2, and 4 mg roIFN tau, respectively, p < 0.01). Recombinant oIFN tau did not affect peak PGFM response to OT (2309 +/- 172 pg/ml; p > 0.1). However, the 4 mg/day dosage delayed the time to peak PGFM (32.4 vs. 47.5 +/- 3.4 min; p < 0.01, 0 vs. 4 mg) and resulted in approximately 200% higher concentrations of PGFM at 60 min post-OT (0 vs. 4 mg/day, p < 0.07). Experiment II was similar to experiment I, except that only the 0- and 4-mg/day dosages of roIFN tau were administered. Ewes were hysterectomized on Day 16, and assay of uterine flushes detected no AVA from ewes treated with either 0 or 4 mg/day roIFN tau. In experiment III, 20 ewes were treated s.c. with either 0, 2, 4, or 6 mg roIFN tau on Day 12. Blood samples, RT, and RR were obtained at frequent intervals for 24 h, and plasma was assayed for progesterone, cortisol, LH, and AVA. Plasma AVA, which increased in a dose-dependent manner, was detectable within 60 min and remained elevated at 24 h compared to control values. RT (elevated 0.5-1.0 degrees C), RR, and cortisol increased in response to all dosages of roIFN tau, with peak values occurring 150-180 min postinjection. For all dosages of roIFN tau, plasma progesterone declined from 120 to 360 min posttreatment and then returned to pretreatment values by 24 h (p < 0.01) as compared to controls. Overall, exogenous roIFN tau altered uterine PGFM response to OT from a pulse to a gradual and sustained elevation and extended IEI with only a transient decline in progesterone and mild hyperthermia, effects that are not expected to compromise pregnancy.

Animals↗
PubMed1997

Interferon tau: a novel pregnancy recognition signal.

PROBLEM: Trophectoderm of ruminant conceptuses (embryo and associated membranes) secretes tau interferons (IFNtau) as the pregnancy recognition signal. How does it act? METHOD: Review of current data. RESULTS: IFNtau acts on uterine epithelium to suppress transcription of the genes for estrogen receptor and oxytocin receptor. This blocks development of the uterine luteolytic mechanism and, therefore, release of luteolytic pulses of prostaglandin F2alpha, but it has no effect on expression of the progesterone receptor. Maintenance of progesterone secretion by the corpus luteum ensures establishment and maintenance of pregnancy. Secretion of IFNtau on days 12-15 for sheep and days 14-17 for cows and goats is essential for pregnancy recognition. CONCLUSION: We propose that IFNtau affects endometrial gene expression by activating the Jak/Stat pathway, which results in formation of the ISGF3alpha transcription factor complex. ISGF3alpha binds to interferon-stimulated response elements and activates transcription of interferon-responsive genes such as interferon regulatory factor-1 (IRF-1) which, in turn, activates expression of the negative-acting transcription factor IRF-2. Pregnancy (or intrauterine injection of roIFNtau) results in a transient increase in endometrial IRF-1 expression followed 36-48 hr later by a sustained increase in IRF-2. We propose that IRF-2, or an IFNtau-induced negative regulatory factor like IRF-2, suppresses expression of the estrogen receptor gene and directly or indirectly blocks expression of the gene for oxytocin receptor to abrogate the uterine luteolytic mechanism and ensure the establishment of pregnancy.

Animals↗
PubMed1997

Effects of stage of gestation and uterine ligation on ovine placentome development and glycosaminoglycans.

Effects of restricting uterine space on physical, biochemical, and histochemical characteristics of ovine placental tissues were studied. Ewes (n = 20) were unilaterally ovariectomized, assigned to either control (C; n = 10) or unilateral (UPx; n = 10) pregnancy groups, mated (d 0), and hysterectomized on either d 60, 90, or 120. Placental and fetal weights and placentome wet weights (PWT) in three placental areas (AI, AII, AIII) were recorded. Placentome tissue concentrations of RNA, DNA, hyaluronic acid (HA), and protein (TP) were determined. Overall, placentome numbers were reduced (P < .02) 23%, but individual PWT increased (P < .05) 27% in UPx ewes. In UPx ewes, neither total placental nor placentome weights, fetal weights, fetal crown-rump lengths, nor PWT:fetal weight ratios were affected by treatment (Trt). In the C and UPx groups, PWT increased (P < .01) from d 60 to 90. However, compensatory growth was confined to placental areas AII and AIII in UPx groups (treatment x area, P < .01). Treatment did not affect concentrations of RNA, DNA, TP, or HA. However, RNA, DNA, and TP increased from d 60 to 120 (P < .01), but HA decreased (P < .01). Histologically, placentome cellularity increased from d 60 to 120 as area occupied by individual fetal chorioallantoic villi (FV) decreased. The FV stained with Alcian Blue 8X. Alcianophilia was attenuated at low pH and eliminated by pretreatment with hyaluronidase, indicating the presence of HA. Thus, increased placentomal cellularity was accompanied by loss of HA from fetal allantoic mesenchyme. Mechanisms regulating loss of HA from FV may support placental maturation and fetal growth.

Animals↗
PubMed1996

Biochemical and immunological properties of related small ruminant trophoblast interferons.

The objectives of this study were 1) to evaluate the biochemical and immunological properties of caprine interferon tau (cIFNtau), 2) to determine if intrauterine injection of recombinant ovine interferon tau (roIFNtau) extends CL life span in goats, and 3) to evaluate potential side effects of intramuscular (i.m.) administration roIFNtau. Caprine IFNtau was purified, and its effects on lymphocyte proliferation were evaluated. Incorporation of 3H-thymidine into newly synthesized DNA was suppressed (P<0.05) by cIFNtau. Spanish goats were also fitted with bilateral uterine catheters at Day 7 or 8 postestrus. The goats received twice-daily intrauterine injections of 100 microg roIFNtau (n = 4) or caprine serum proteins (n = 4) from Days 14 to 18 postestrus. Intrauterine injection of roIFNtau extended CL life span compared with that of control goats (26.4 +/- 1.7 vs 17.8 +/- 1.9 d, respectively; P<0.01). Potential side effects of intramuscular injections of roIFNtau were also evaluated. Goats received 0, 1, 2 or 4 mg of roIFNt on Days 10, 13, 16 or 19 of the estrous cycle. Treatment of goats with roIFN resulted in hyperthermia (P<0.01), with rectal temperatures of 40.5 degrees C recorded after 4 h and returning to normal (38.5 degrees C) after 24 h. Concomitant with the increase in rectal temperatures was a decrease (P<0.01) in plasma progesterone concentrations. Therefore, the tau interferons of goats and sheep have similar biological properties and roIFNtau has side effects associated with other classes of interferons.

Journal Article↗
PubMed1996

Effects of interferon-tau and progesterone on oestrogen-stimulated expression of receptors for oestrogen, progesterone and oxytocin in the endometrium of ovariectomized ewes.

The effects of recombinant ovine interferon-tau (IFN-tau) and progesterone on oestrogen-stimulated expression of endometrial receptors for oestrogen (ER), progesterone (PR) and oxytocin (OTR) were determined in ovariectomized ewes. Cyclic ewes (n = 16) were ovariectomized and fitted with uterine catheters on Day 4 of the oestrous cycle (Day O, oestrous) and assigned randomly in 2 x 2-factorial arrangement to receive daily intrauterine injections of either recombinant ovine IFN-tau (roIFN-tau; 2 x 10(7) anti-viral units) or control proteins from Day 11 to Day 15 and 50 mg progesterone from either Day 4 to Day 10 (E-P) or Day 4 to Day 15 (E+P). All ewes received 50 micrograms oestradiol-17 beta on Days 13, 14 and 15 and were hysterectomized on Day 16. In control ewes, endometrial ER mRNA, PR protein and OTR density were greater in E-P- than E+P- treated ewes. In E-P ewes, roIFN-tau decreased oestrogen-stimulated increases in ER and OTR, but not PR expression compared with control ewes. In E+P ewes, endometrial ER mRNA and protein, PR mRNA and protein, and OTR levels were lower in roIFN-tau-treated ewes than control ewes. Immunoreactive ER and PR were absent in the endometrial luminal and superficial glandular epithelium of roIFN-tau compared with control ewes, but were present in the deep glandular epithelium and stroma regardless of steroid or protein treatment. These results indicate that progesterone affects oestrogen-induced increases in endometrial ER, PR and OTR expression in the PR+ deep glandular epithelium and stroma, whereas IFN-tau suppresses oestrogen-induced increases ER, PR and OTR expression in the PR- luminal and superficial glandular epithelium. These combined actions of IFN-tau and progesterone to suppress oestrogen-induced increases in endometrial OTR formation would prevent pulsatile production of luteolytic prostaglandin F2 alpha by the endometrium during early pregnancy.

Animals↗
PubMed1996

High yield expression and secretion of the ovine pregnancy recognition hormone interferon-tau by Pichia pastoris.

The early conceptus (embryo and associated membranes) of domestic ruminats signals its presence to the maternal uterus through production of interferon-tau (IFN-tau). Production of IFN-tau ensures continued production of progesterone, the hormone of pregnancy, by the ovarian corpus luteum. This paper reports the high-level expression and efficient secretion of biologically active recombinant ovine IFN-tau (rOvIFN-tau) by Pichia pastoris. The developed method produces more than 80% pure recombinant ovine IFN-tau, obviating the need for further purification for many purposes. Initial fermentation studies produced IFN-tau at 280 mg/liter and demonstrate the potential of this system for large-scale production of IFN-tau.

Animals↗
PubMed1996

Enzyme-linked immunosorbent assay for ovine interferon-tau.

Ovine interferon-tau (OvIFN-tau) is a trophectoderm secretory protein responsible for maintenance of corpus luteum function during early pregnancy. Methods for its quantitation include an antiviral assay and radioimmunoassay (RIA), both of which have disadvantages. We therefore developed an ELISA for OvIFN-tau that is specific, rapid, and 40-fold more sensitive than the current RIA. It uses a monoclonal antibody (Ab) HL129, which binds both native and recombinant (r) OvIFN-tau. The ELISA accurately detected known amounts of rOvIFN-tau added to yeast and tissue culture medium and to sheep serum at concentrations between 0.005 and 50,000 ng/ml. Inter- and intraassay coefficients of variation were 9.3 +/- 0.8 and 6.1 +/- 1.4%, respectively. Data are given for the reliability and reproducibility of the ELISA for measuring native OvIFN-tau and rOvIFN-tau.

Animals↗
PubMed1996

Effects of recombinant interferon-tau on ovine lentivirus replication.

As a pregnancy recognition signal, sheep trophoblast cells secrete a type I interferon, ovine interferon-tau (OvIFN-tau), which has potent antiviral activity. We studied the effects of a recombinant protein (rOv-IFN-tau) on the replication of ovine lentivirus (OvLV) in goat synovial membrane cells. The amount of provirus DNA, as measured by polymerase chain reaction (PCR), the virus titers, and the number of OvLV-induced syncytia were 76.5%, 82%, and 95%, respectively, lower in cultures treated with rOv-IFN-tau than in placebo-treated controls (p < 0.01). rOv-IFN-tau also reduced OvLV reverse transcriptase activity and protected cells from OvLV-induced cell lysis, but the effect was less dramatic. The antiviral activity increased with the concentration up to a maximum with 256 antiviral units of rOv-IFN-tau per ml.

Animals↗
PubMed1996

Placental interferons.

Trophectoderm of ruminant conceptuses (embryo and associated membranes) secrete tau interferons (IFN tau) as the pregnancy recognition signal. Secretion of IFN tau on gestational days 12-13 for sheep and gestation days 14-17 for cows and goats is critical for pregnancy recognition. IFN tau acts on uterine epithelium to suppress estrogen receptor and oxytocin receptor gene expression, which prevents uterine release of luteolytic pulses of prostaglandin F2 alpha (PGF). Expression of the progesterone receptor (PR) gene in uterine endometrium is not affected by oIFN tau. Maintenance of progesterone secretion by the corpus luteum (CL) ensures establishment of pregnancy. Pig conceptuses secrete both IFN alpha and IFN gamma between days 15-21 of gestation, but their role(s) in early pregnancy is unknown. Estrogen secreted by pig trophoblast between gestational days 11-13 and 15-25 increases endometrial receptors for prolactin and causes exocrine secretion of PGF into the uterine lumen to prevent luteolysis. Shared cell-signaling mechanisms by IFNs and lactogenic hormones through Janus kinases (JAK) 1 and 2 may provide a common pathway to abrogate luteolytic mechanisms to ensure establishment of pregnancy. The role(s) of IFNs produced by human and rodent placentae is not known.

Animals↗
PubMed1995

Intrauterine injection of ovine interferon-tau alters oestrogen receptor and oxytocin receptor expression in the endometrium of cyclic ewes.

This study determined the effects of intrauterine injections of recombinant ovine interferon-tau; (roIFN-tau; 2 x 10(7) antiviral units/day) or control proteins (6 mg/day) from day 11 to day 14 post-oestrus = day 0) on endometrial expression of receptors fro oestrogen, progesterone and oxytocin in cyclic ewes. Plasma concentrations of progesterone were greater on day 15 in ewes receiving roIFN-tau compared with control proteins (P < 0.02, treatment x day). Ewes injected with roIFN-tau had lower endometrial levels or oestrogen receptor mRNA (P > 0.10) and protein (P < 0.01) on day 15 compared with ewes receiving control proteins. In situ hybridization analysis indicated that oestrogen receptor mRNA was more abundant in the luminal and glandular epithelium of control ewes compared with roIFN-tau-treated ewes. Immunoreactive oestrogen receptor was also present in the luminal and glandular epithelium of control, but not roIFN-tau-treated ewes. Endometrial levels of progesterone receptor mRNA and protein were not different (P > 0.10) between control and roIFN-tau-treated ewes. In situ hybridization analyses indicated that progesterone receptor mRNA abundance was low in endometrial epithelium and stroma of both control and roIFN-tau-injected ewes. Immunoreactive progesterone receptors were present in the endometrial stroma and epithelium of control ewes, but confined to the stroma of roIFN-tau-treated ewes. Oxytocin receptor density was lower (P < 0.01) in the endometrium of ewes injected with roIFN-tau than control proteins; however, oxytocin receptor affinity was not affected (P > 0.10) by treatment. Concentrations of 13,14-dihydro-15-ketoprostaglandin F2a (PGFM) were not increased by exogenous oxytocin administration in control and roIFN-tau-treated ewes on days 10 or 12 post-oestrus. However, on day 14, control ewes responded to oxytocin with increased plasma concentrations of PGFM, whereas ewes receiving roIFN-tau remained unresponsive to oxytocin. These results indicate that the an tiluteolytic effects of IFN-tau are to prevent increases in endometrial oestrogen receptor MRNA and protein and oxytocin receptor density which abrogates uterine release of prostaglandin F2a during maternal recognition of pregnancy. IFN-tau may inhibit the synthesis of oestrogen receptor mRNA by a transcriptional or post-transcriptional regulatory mechanism to suppress oxytocin receptor formation during early pregnancy in ewes.

Analysis of Variance↗
PubMed1995

Extension of corpus luteum lifespan and reduction of uterine secretion of prostaglandin F2 alpha of cows in response to recombinant interferon-tau.

Two experiments tested the effect of recombinant ovine and bovine interferon-tau on corpus luteum lifespan, interestrous interval, and oxytocin-induced uterine secretion of prostaglandin F2 alpha. Cows received intrauterine injections of 100 micrograms of recombinant ovine interferon-tau plus 1.4 mg of BSA or of 1.5 mg of BSA alone in Experiment 1 and 200 micrograms of recombinant bovine interferon-tau plus 1.3 mg of BSA or 1.5 mg of BSA alone in Experiment 2. Twice daily injections (0700 and 1900 h) were split evenly between the uterine horns from d 14 to 24 of the experimental estrous cycle via an AI pipette in Experiment 1 and via intrauterine catheters in Experiment 2. On d 17, cows were injected with 100 IU of oxytocin, and plasma was collected for analysis of 13,14-dihydro-15-keto-prostaglandinF2 alpha. Recombinant ovine interferon-tau extended the lifespan of the corpus luteum (27.5 vs. 19.2 d) and interestrous interval (30.5 vs. 20.6 d) and abolished the oxytocin-induced increase in 13,14-dihydro-15-keto-prostaglandinF2 alpha, which peaked at 30 min for the BSA control group (210.8 pg/ml). Recombinant bovine interferon-tau also extended the lifespan of the corpus luteum (29.0 vs. 21.4 d) and interestrous interval (31.5 vs. 22.6 d) and abolished the oxytocin-induced increase in 13,14-dihydro-15-keto-prostaglandin F2 alpha, which peaked at 30 min for the BSA control group (205.6 pg/ml). In conclusion, recombinant ovine interferon-tau and recombinant bovine interferon-tau were effective antiluteolytic agents in cattle.

Animals↗
PubMed1994

Structure/function studies with interferon tau: evidence for multiple active sites.

A novel interferon (IFN), called IFN-tau (IFN-tau), has recently been discovered and has been shown to be a pregnancy recognition hormone. Unlike known IFNs, however, IFN-tau exhibits high antiviral and antiproliferative activity without cytotoxicity. The structural basis for IFN-tau function has been examined using six overlapping synthetic peptides corresponding to the entire ovine (Ov) IFN-tau sequence. Four peptides representing amino acids 1-37, 62-92, 119-150, and 139-172 inhibited OvIFN-tau antiviral activity in a dose-dependent manner. Polyclonal antipeptide antisera directed against the same four peptides blocked OvIFN-tau binding and antiviral activity, confirming the specificity of the peptide competitions. Because IFN-tau and IFN-alpha both interact with the type I IFN receptor, peptide inhibition of bovine and human IFN alpha activity was also determined. Of importance, only three peptides, OvIFN-tau (62-92), (119-150), and (139-172) inhibited IFN-alpha antiviral activity. The amino-terminal IFN-tau peptide, OvIFN-tau(1-37), was not inhibitory. These data suggest that the internal and carboxy-terminal reactive domains of IFN-tau may interact with a common type I IFN site on the receptor, while the amino terminus interacts with a site that elicits activity unique to OvIFN-tau. Finally, the antiproliferative activity of OvIFN-tau was localized primarily to the broad carboxy-terminal region, with OvIFN-tau(119-150) being the most effective inhibitor of OvIFN-tau-induced reduction of cell proliferation. Thus, multiple domains of IFN-tau have functional significance.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗