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S Lundin-Schiller

Publications and source records attributed to S Lundin-Schiller.

12 recordsLinked to original sources

Characterization of porcine endometrial, myometrial, and mammary oxytocin binding sites during gestation and labor.

Changes in oxytocin (OT) receptor expression have been found to be an important determinant of the physiological effect of OT in several species. To date there are no published studies of OT binding sites during pregnancy in the pig. The purpose of the present study is to improve understanding of the role of OT in porcine parturition. The concentration and affinity of OT binding sites were determined for myometrium and endometrium from pregnant and postpartum gilts. Tissues were obtained after slaughter from 7 animals in each of four groups: 1) 90 days gestation, 2) 112 days gestation, 3) term after milk letdown (before delivery), and 4) within 1-3 h after farrowing. Mammary tissues were obtained for some animals in each group (n = 3-5/group). Before slaughter, blood was collected from each animal and assayed for estradiol-17 beta, progesterone, 13,14-dihydro-15-keto-prostaglandin F2 alpha (PGFM), and OT. Binding of 3H-OT in the three tissues was concentration- and time-dependent. Sites of 3H-OT binding (fmol/mg protein +/- SEM) increased toward term for each tissue and remained elevated in the postpartum group. Endometrial and mammary tissues displayed the most acute increases in OT binding site concentrations while myometrial tissues displayed a more gradual increase in OT binding sites over the times studied. The binding sites displayed high affinity for 3H-OT and were characterized by linear Scatchard plots. Concentrations of estradiol-17 beta, PGFM, and OT (pg/ml +/- SEM) were positively correlated with 3H-OT binding site concentrations, whereas progestrone concentrations (ng/ml +/- SEM) were negatively correlated with binding site concentration, as determined by Pearson's Correlation Analysis. The data represent the first account of changes in the expression of OT binding sites on porcine tissues during gestation and labor.

Animals↗

Biosynthesis of interleukin-6 by cultured human chorion laeve cells: regulation by cytokines.

Intrauterine infection is an important cause of preterm labor and delivery and is characterized by increased production of inflammatory cytokines by gestational tissues. We evaluated the biosynthesis of the inflammatory cytokine interleukin-6 (IL-6) by human chorion laeve cells and its regulation by other cytokines essential to the inflammatory process. We found that cultured chorion cells secrete IL-6 in the presence of growth medium supplemented only with 10% fetal calf serum. IL-1 beta, tumor necrosis factor, and lipopolysaccharide all induced a significant concentration-dependent stimulation of IL-6 production by chorion cells. The concentration range of each cytokine tested (0.1-10 ng/mL) is within the range of values found in the amniotic fluid of women destined to deliver preterm due to infection of gestational tissues. Additionally, treatment of chorion cells with IL-1 beta in combination with actinomycin-D or cycloheximide attenuated the stimulatory action of IL-1 beta on IL-6 production. Northern blot analysis of total RNA from cultured chorion cells stimulated with IL-1 beta demonstrated that IL-6 mRNA increases over time. Our data suggest that IL-6 is produced by human fetal chorion in response to infection of maternal gestational tissues. In conjunction with other inflammatory mediators, fetally derived IL-6 may play a role in the pathophysiology of preterm labor due to infection.

Blotting, Northern↗

Endothelin production by amnion and its regulation by cytokines.

Cells derived from human amnion, an avascular tissue, produced significant amounts of endothelin 1 and 2, although the rate of biosynthesis was approximately one tenth of that of human umbilical vein endothelial cells. Endothelin 1 and 2 was not produced in measurable amounts by cells derived from chorion laeve or decidua. Production of endothelin 1 and 2 by amnion cells was increased by treatment with the cytokines interleukin-1 beta, tumor necrosis factor, and interleukin-6. The biosynthesis of endothelin 1 and 2 by an avascular tissue is suggestive of a wider role for endothelins than has been recognized.

Amnion↗

Isolation of multiple substances in amniotic fluid that regulate amnion prostaglandin E2 production: the effects of gestational age and labor.

The present study was undertaken to evaluate the effects of whole amniotic fluid (AF) and fractions of AF on amnion cell prostaglandin E2 (PGE2) production. Amnion cells were grown to confluence and then incubated in the presence of AF, or fractions thereof, obtained at 17-19 weeks gestation (MID), at term prior to the onset of labor (NIL), and at term after spontaneous onset of labor (LABOR). All whole AFs were stimulatory to amnion cell PGE2 production (p less than 0.001) but the stimulation by NIL and LABOR AFs was significantly greater (p less than 0.001) than stimulation by the MID AF. Fractionation of the AFs from the three groups (n = 9-10 per group) revealed multiple discernable peaks of stimulatory activity in each group. The majority of peaks had retention times that were similar among the three groups, and peak stimulatory activities were greater in NIL and LABOR samples than in MID samples.

Amnion↗

Epidermal growth factor and the regulation of amnion prostaglandin biosynthesis.

The production of prostaglandins by amnion is a key factor in the mechanism of human parturition yet the regulation of prostaglandin biosynthesis in amnion is poorly understood. Hence, we have investigated the regulation of epidermal growth factor (EGF) stimulation of prostaglandin biosynthesis in human amnion cells. This stimulatory action is inhibited by cycloheximide or actinomycin D at high concentrations, but enhanced at much lower concentrations of these protein synthesis inhibitors. An amnion-produced prostaglandin inhibitor or immediate early gene action may explain these effects. Pretreatment with phorbol esters (inhibition of protein kinase C activity) reduces basal prostaglandin production and attenuates the stimulatory action of EGF on prostaglandin biosynthesis. Hence, amnion prostaglandin biosynthesis is dependent partly on protein kinase C activity.

Amnion↗

Renin increases human amnion cell prostaglandin E2 biosynthesis.

Chorionic cells are known to produce several protein hormones; among them is prorenin/renin, whose function is unknown at this time. Amnion is contiguous with chorion and plays a part in the mechanism(s) of parturition through increased prostaglandin (PG) production. The purpose of the present study was to determine whether renin has any action on amnion cell PGE2 biosynthesis. Amnion cells in primary monolayer culture were incubated for 16 h with increasing concentrations of renin. Renin induced a concentration-dependent increase in amnion cell PGE2 production (e.g. in picograms of PGE2 per microgram protein/16 h; mean +/- SEM; n = 4; control, 3.01 +/- 0.15; 0.0001 U/mL renin, 9.66 +/- 2.0; 0.001 U/mL renin, 10.36 +/- 1.91; 0.01 U/mL renin, 10.3 +/- 3.36; 0.1 U/mL renin, 13.82 +/- 2.1). Significant stimulation of amnion cell PGE2 by renin is not observed until 2 h of incubation; stimulation continues a further 6 h, with little change in the following 8 h. We tested the possibility that renin's stimulatory effects were due to angiotensin-I (AI) and angiotensin-II (AII) formation by testing the effects of AI and AII directly and that of renin in the presence of saralasin, a potent antagonist of AII action. Saralasin did not inhibit the effect of renin, nor was AI or AII alone (10(-10)-10(-6) M) stimulatory. Thus, we believe that chorionic renin may have a novel role in the regulation of amnion cell PGE2 production that is independent of angiotensin formation.

Amnion↗

Amnion cell prostaglandin E2 stimulatory activity in chorion laeve-conditioned medium.

In this study we demonstrate the presence of a stimulant(s) to amnion cell prostaglandin (PG) E2 production in chorion-conditioned medium (CCM). The CCM induced a dose-dependent increase in amnion cell PGE2 production. This stimulatory activity was eliminated by heat and protease treatment. Maximal stimulation of amnion PGE2 by CCM did not occur until after 2 h of incubation, and treatment with cycloheximide (1 microgram/ml) effectively eliminated the ability of the amnion cells to respond to CCM. Additionally, CCM and arachidonic acid (2-40 microM) were synergistic in their stimulatory actions on amnion PGE2 production. CCM-treated amnion cells recover more quickly from acetylsalicylic acid pretreatment as compared to control. It is concluded that CCM contains a heat-labile protein which stimulates amnion cell PGE2 production by induction of prostaglandin endoperoxide synthase activity.

Amnion↗

Prostaglandin production by human chorion laeve cells in response to inflammatory mediators.

Cytokines produced during an intrauterine infection may cause increased prostaglandin production and thus preterm labor. Previously, we have shown that cytokines increase prostaglandin production by human amnion and decidual cells. In the present study we examined the effect of interleukin-1 beta (IL-1 beta), tumor necrosis factor (TNF), and endotoxin on prostaglandin production by chorion laeve cells. Upon reaching confluence at day 3 and after 10 days in culture, human chorion laeve cells in primary culture were incubated with each substance. On day 3 of culture the chorion cells demonstrated limited responsiveness to the test agents with a maximum response of less than two times basal production. However, after 10 days the cultures were highly responsive to the test agents with maximum responses of greater than ten times basal production. We conclude that early in culture chorion cells may express fewer functional receptors for the test agents. Alternatively, a subpopulation of chorion cells responsive to cytokines and endotoxin may predominate by day 10 of culture. Chorion laeve, therefore, could contribute to the increased intrauterine prostaglandin production associated with infection-driven preterm labor.

6-Ketoprostaglandin F1 alpha↗

Regulation of chorion laeve prostaglandin E2 production by epidermal growth factor, protein kinase C activation and calcium.

The effects of epidermal growth factor (EGF), phorbol 12-myristate 13-acetate (PMA), A23187, and ionomycin on prostaglandin production by chorion laeve cells in culture for 3 days and 10 days were tested. Experiments were conducted at day 3 because at this time the cultures became confluent and again at day 10 because changes have been observed in the biochemical properties of these cells with time in culture. At 3 days of culture the cells did not respond to EGF but at 10 days EGF (10 ng/ml) induced a significant increase in prostaglandin E2 production. PMA (10(-9) to 10(-6) M) induced a significant increase in PGE2 production at both times in culture. The calcium ionophores, A23187 and ionomycin, were less effective in eliciting a response at either time in culture. Only A23187 (1 microM) induced a significant increase in PGE2 production at day 10 of culture. These data suggest that the presence of functional EGF receptors may increase with time in culture. Furthermore, activation of the protein kinase C pathway in the chorion laeve stimulates prostaglandin biosynthesis. On the other hand, chorion laeve cell prostaglandin biosynthesis is not responsive to increases in intracellular calcium induced by mobile ion carriers such as the ionophores used in this study.

Calcimycin↗

Mechanism of interleukin-1 beta stimulation of human amnion prostaglandin biosynthesis: mediation via a novel inducible cyclooxygenase.

We have evaluated the mechanism by which interleukin-1 beta (IL-1 beta) increases amnion cell PGE2 production in a concentration-dependent manner. IL-1 beta-stimulated amnion cell PGE2 biosynthesis was time-dependent, and significant stimulation occurred within 2 h of incubation. IL-1 beta stimulation occurred in the presence of added arachidonic acid but was abrogated by treatment with cycloheximide and actinomycin D. Amnion cells treated with IL-1 beta recovered rapidly from aspirin pretreatment suggesting an action on fatty acid cyclooxygenase (COX). Increased amounts of COX protein were demonstrated by Western blot analysis within 2 h of IL-1 beta treatment of amnion cells. Northern blot analysis using a probe specific for a novel form of COX (COX-II) showed an increase in mRNA for this COX within 30 min. This finding using a homologous detection system and human cells of fetal origin in primary culture provides strong support for a physiological role for COX-II in man.

Amnion↗