Functions of Macrophages in Human Decidual Tissue in Early Pregnancy

PROBLEM: Roles of decidual macrophages (DMs) in the maintenance of early pregnancy was determined by comparing three of their functions, antigen presentation, immunoregulation, and lymphokine production, with those of peripheral monocytes (PMos) isolated from the same subjects. METHOD: The antigen-presenting capacity of DMs was examined by the one-way mixed lymphocyte reaction (MLR) in which accessory cell-depleted mononuclear cells isolated from pregnant women were used as responders. The effect of DMs on cellular immunity was investigated by inhibition tests of either one-way MLR or phytohemagglutinin stimulation. The production of interleukin-1 (IL-1) and prostaglandin E₂ (PGE₂) by DMs following lipopolysaccharide stimulation was examined. RESULTS: Addition of increasing concentrations of DMs to the culture resulted in a concentration-dependent proliferative response, as well as with PMos. In both assays, a stronger suppression was observed in the presence of DMs from normal pregnant women compared with PMos from the same subjects. DMs were found to secrete significantly lower levels of IL-1 α and IL-1β than PMos. No difference in PGE₂ production was observed between DMs and PMos. CONCLUSIONS: These findings suggest that DMs present in human early decidual tissue have a capacity for allo-antigen presentation, a higher suppressive activity, and a lower capacity to produce IL-1 than their peripheral counterparts.     

Effect of indomethacin and prostaglandin E2 on structural differentiation of rat endometrium during artificially induced decidualization

Morphological differentiation of uterine stromal and luminal epithelial cells was studied in steroid-injected ovariectomized rats following unilateral intrauterine instillation of sesame oil, phosphate-buffered saline containing gelatin (PBSG), PBSG + indomethacin (IM; an inhibitor of prostaglandin synthesis), or PBSG + IM + prostaglandin E₂ (PGE₂). The latter two treatments were preceded by a subcutaneous injection of IM. Uteri were examined by light and electron microscopy at intervals between 8 and 120 hr (n = 4/treatment/time). Differentiation began in the periluminal antimesometrial region and progressed peripherally and towards the mesometrial aspect in all groups. Structural features and timing of differentiation were similar for oil-injected and PBSG-infused uteri. Administration of IM inhibited the onset of the decidual cell reaction and had deleterious effects on the luminal epithelium. Inclusion of PGE₂ in the instillate accelerated stromal cell differentiation and overcame the inhibitory effects of IM. The results implicate prostaglandins, particularly PGE₂, in endometrial transformation during decidualization.     

Mechanisms of chorioamnionitis‐associated preterm birth: interleukin‐1β inhibits progesterone receptor expression in decidual cells

In chorioamnionitis (CAM), a major cause of preterm birth (PTB), maternal–fetal inflammation of the decidua and amniochorion cause the release of cytokines that elicit cervical ripening, fetal membrane rupture and myometrial activation. We posit that this inflammatory milieu triggers PTB by inhibiting progesterone receptor (PR) expression and increasing decidual prostaglandin (PG) production. Immunohistochemical staining of decidua detected significantly lower PR levels in decidual cells (DCs) from CAM‐complicated PTB. Incubation of DCs with IL‐1β decreased PR expression and significantly increased PGE₂ and PGF_2α production and COX‐2 expression. The addition of PGF_2α to DC cultures also suppressed PR expression. However, the COX inhibitor, indomethacin, did not reverse IL‐1β suppression of PR expression in DC cultures. Although IL‐1β treatment activated the NF‐K B, ERK1/2 and p38 MAPK signalling cascades in DCs, inhibition of ERK1/2 MAPK signalling alone was sufficient to completely reverse the suppression of PR levels by IL‐1β. These findings suggest that CAM‐associated PTB is induced at least in part by IL‐1β‐mediated functional progesterone withdrawal. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Uterine circulatory dysfunction induced by whole-body vibration and its endocrine pathogenesis in the pregnant rat

Effects of whole-body vibration on normal pregnancy were studied in the rat. Uterine blood flow and five endocrine functions corticosterone (CS), estradiol (E₂), progesterone (P), prostaglandin E₂ (PGE₂) and prostaglandin F₂ (PGF₂) concentration were measured in rats exposed to whole-body vibration with an acceleration of 10 m·s^–2 at a frequency of 8 Hz. While no change in uterine blood flow was observed in control rats, uterine blood flow was significantly decreased 75 and 90 min after exposure to vibration. The uterine blood flow at 15 and 30 min was increased by pretreatment with intraperitoneal injections of angiotensin 11 (AII). In contrast, in AII pretreated rats exposed to the vibration, uterine blood flow was significantly reduced 90 min after exposure. The CS concentration was increased by vibration independently of the pretreatment with All. Neither E₂ nor PGF₂ concentration were changed by the vibration with or without AII administration. The P and PGE₂ concentrations were both decreased by vibration in the absence of AII, while the decrease in PGE₂ induced by the vibration was also found in AII-treated rats. The present results indicated that the pregnant rats subjected to whole-body vibration responded with changes in uterine and ovarian function. The observed decrease in uterine blood flow may have been the result of reduced PGE₂ concentration resulting from an indirect effect of vibration.     

The Role of Trophoblast Interferons in the Maintenance of Early Pregnancy in Ruminants

PROBLEM: Are the effects of ruminant trophoblast interferon-tau (IFN-τ) on uterine prostaglandin (PG) secretion a specific action of this cytokine and what are the effects of IFN-τ on expression of uterine genes not generally associated with pregnancy maintenance? METHODS: The effects of IFN-τ and IFN-α on bovine uterine expiant and epithelial cell production of PGF_2α and PGE₂ were determined in the presence and absence of oxytocin (OT). The effects of intrauterine administration of IFN-τ were determined on uterine expression of retinol-binding protein (RBP) and transforming growth factor-beta (TGF-β) isoforms. RESULTS: IFN-τ attenuated uterine endometrial secretion of PGF_2α and PGE₂ in vitro and diminish PG stimulation by OT. IFN-τ and IFN-α were observed to be equipotent. Intrauterine infusion of IFN-τ resulted in a significant decrease in steady-state RBP mRNA levels and expression of TGF-B1, 2, and 3 mRNA levels were lowest in IFN-τ treated animals. CONCLUSION: Negative regulation of gene expression may be a general strategy in IFN activity. This may explain the similar activities of IFN-τ and IFN-α on a broad variety of cell types, including ruminant uterine endometrium.     

Human Fetal/Neonatal Suppressor Activity: Relation Between OKT Phenotypes and Sensitivity to Prostaglandin E2 in Maternal and Neonatal Lymphocytes

ABSTRACT: T lymphocytes from human fetuses and newborns strongly and spontaneously suppress various adult cell functions (i.e. T-cell proliferation, B-cell differentiation, and Ig synthesis). The precise phenotype of the suppressor cell is controversial. In this investigation we use cord T-cell subsets negatively selected by the panning technique or by complement-mediated lysis using the monoclonal antibodies OKT4 and OKT8. Cord T cells deprived of the OKT4⁺ subpopulation exerted only a marginal suppressor activity (12 ± 7 as compared to 73 ± 4% of unfractionated T cells) on the proliferation of maternal cells in our PHA-stimulated co-culture assay using sex chromosomes as markers for dividing cord (male) and maternal cells. The suppressive effect was direct, i.e. not mediated by induction of maternal OKT8⁺ suppressor effector cells. Cord and maternal T-cell subsets were also tested for their sensitivity to exogenous prostaglandin E₂ (PGE₂) at doses varying between 1.4 × 10^?5 and 1.4 × 10^?9 M. Both maternal OKT4^? and OKT8^? T-cell subsets were highly sensitive to suppression by PGE₂. In contrast, cord OKT8^? T cells were essentially nonsensitive at all doses of PGE₂ used, whereas cord OKT4^? T cells were significantly suppressed at four out of five concentrations tested (1.4 × 10^?6 through 1.4 × 10^?9). Our results suggest a direct correlation between the phenotypes of the cord-suppressor and maternal-target T cells and their sensitivity to PGE₂.     

Tumour Growth Causes Suppression of Autoreactive T-Cell Proliferation by Disrupting Macrophage Responsiveness to Interferon-γ

Normal immune homeostasis is regulated partly by a small population of CD4⁺ T cells that react to autologous major histocompatibility complex class-II molecules on self-cells. Decreased autoreactive T-cell responses are associated with cancer. Tumour growth causes syngeneic macrophages (Mø) to suppress autoreactive T-cell proliferation by decreasing Mø class-II expression and increasing Mø production of the suppressor molecule prostaglandin E₂ (PGE₂). Because interferon-γ (IFN-γ) is a potent Mø activation molecule which regulates both Mø PGE₂ and class-II expression, the effects of IFN-γ on tumour-induced suppression of autoreactive T-cell proliferation were investigated. Exogenous IFN-γ increased normal host (NH) CD4⁺ autoreactive T-cell proliferation stimulated by syngeneic NHMø but decreased proliferation stimulated by tumour-bearing host (TBH) Mø. Antibody (Ab) neutralization of endogenous IFN-γ activity reduced TBH Mø-mediated suppression. Kinetic studies showed that endogenous IFN-γ suppressor activity was not exclusive during T-cell activation. Indomelhacin treatment blocked IFN-γ-induced suppression in TBH Mø-T cell cultures. TBH Mø-T cell cultures contained significantly more PGE₂ than those containing NH Mø. Exogenous IFN-γ increased early PGE₂ production in TBH Mø cultures but decreased production in NHMø cultures. The Ab-mediated neutralization of endogenous transforming growth factor-β or tumour necrosis factor-x reduced TBH Mμ-mediated suppression and blocked IFN-γ-induced suppression. Short-term treatment of Mμ with IFN-γ before their addition to T cells caused TBH Mμ to stimulate T-cell proliferation, which suggests that early suppressor molecule production by TBHMø inhibits synthesis or activity of IFN-γ-induced stimulatory monokines. These results show that tumour growth causes Mø to suppress autoreactive T-cell responses by allowing IFN-γ to induce Mø suppressor molecules, which block production or activity of stimulatory monokines.     

Comparison of PGE2, 6-keto PGF1α and renin release from dog kidneys

Several renal cell types synthesize prostaglandin E₂ (PGE₂) and prostacyclin (PGI₂). To examine whether the release of these prostaglandins varies in proportion, prostaglandin synthesis was stimulated in anaesthetized dogs by renal arterial constriction, ureteral occlusion, intrarenal angiotensin II infusion and infusion of arachidonic acid, the precursor of PG synthesis. PGI₂ was measured as its stable hydrolysed product, 6-keto PGF_1α. The two former procedures raised PGE₂ release to 13 ± 2 pmol min^-1, 6-keto PGF_1α release to 5 ± 2 pmol min^-1 and renin release to 23 ± 5 μg AI min^-1, Angiotensin II infusion, reducing the renal blood flow by 30%, increased PGE₂ and 6-keto PGF_1α release only half as much as ureteral and renal arterial constriction, and exerted no significant effect on renin release. By increasing the infusion rate of angiotensin II up to 10 times, the renal blood flow remained unaltered in four dogs and fell to 50% of control in two dogs, but PGE₂ and 6-keto PGF_1α release did not increase further in any of the experiments. Arachidonic acid, infused at 40 and 160 μg kg^-1 min^-1, increased prostaglandin release in proportion to the infusion rate. At the highest infusion rate, PGE₂ release averaged 166± 37 pmol min^-1 and 6-keto PGF_1α release 98 ± 28 pmol min^-1. All procedures increased PGE₂ and 6-keto PGF_1α release in a fixed proportion of about 2.5:1, whereas renin release increased only during autoregulatory vasodilation.     

Prostaglandins and corticosterone in the oviparous female lizard,Podarcis sicula sicula,during reproduction

The in vitro effects of prostaglandin F_2α (PGE_2α) and prostaglandin E₂ (PGE₂) on corticosterone release by ovarian follicles, corpora lutea (CL), and interrenals were studies in the female lizard, Podarcis sicula sicula, during reproduction. Follicles and CL were divided according to their different development stages: follicles: pre-vitellogenic, early-vitellogenic, mid-vitellogenic and fully-grown; CL: CL 1 (unshelled eggs in the oviducts), CL2 (shelled eggs in the oviducts), CL3 (eggs laid 6 h previously) and CL4 (eggs laid 48 h previously). Interrenals were divided according to the reproductive stages: pre-vitellogenesis, vitellogenesis, ovulation, post-ovulation, and post-deposition. PGF_2α release was highest in fully-grown follicles and PGE₂ in early-vitellogenic follicles, corticosterone was highest in pre-vitellogenic and lowest in early-vitellogenic follicles. PGE₂ decreased corticosterone in pre-vitellogenic, mid-vitellogenic and fully-grown follicles. PGE_2α release was highest in CL4, and PGE₂ in CL1 and CL2, CL3. In interrenals, PGE_2α release was highest and PGE₂ lowest during ovulation, corticosterone was highest in CL4. PGF_2α increased and PGE₂ decreased interrenal corticosterone during vitellogenesis, ovulation, and post-ovulation. In the plama, PGF_2α levels were highest and PGE₂ lowest during ovulation, corticosterone was highest during ovulation. These results suggest that corticosterone, modulated by PGF_2α and PGE_2α, is implied in the reproductive processes with different roles. In fact this steroid could favour ovulatory and luteolytic processes. In addition the hypothesis of an anti-vitellogenic role of corticosterone in discussed.     

Alterations in prostaglandin synthesis during senescence of human lung fibroblasts

Prostaglandin (PG) synthesis by human embryo lung fibroblasts in culture was determined with increasing population doubling. These cultures synthesized PGE₂, PGF_2α, PGI₂ (prostacyclin) and TXA₂ (thromboxane A₂) in response to fetal bovine serum or ascorbic acid. Changes in prostaglandin synthesis by these cells during aging were observed in response to serum or ascorbic acid. These included a shift from the synthesis of PGI₂ and PGE₂ to TXA₂ and PGF_2α and finally to PGF_2α alone. We also observed a marked increase during aging in the release of precursor fatty acid from lipid stores upon stimulation with ascorbic acid. A parallel decrease in the ability to convert the released fatty acid to prostaglandins was detected.     

PGE2 Contributes to In vitro MSC‐Mediated Inhibition of Non‐Specific and Antigen‐Specific T Cell Proliferation in MS Patients

Current theories of multiple sclerosis (MS) induction and progression place autoreactive T cells in the focus of the pathogenesis. Mesenchymal/stromal stem cells (MSC) have become a promising alternative approach for pathogenic therapy of MS due to their immunomodulatory properties, underlying mechanisms of which are intensive study. The objective of the research was to investigate the contribution of PGE₂ to MSC‐mediated suppression in patients with MS using in vitro model of mitogen‐ and myelin‐stimulated T cell cocultivation with autologous/allogeneic MSC. We have showed that PGE₂ production depends on cell‐to‐cell contact of MSC and lymphocytes. The antigenic stimulation did not affect PGE₂ production following cocultivation of MSC and PBMC, and it is the presence of MSC in cell culture that significantly increases PGE₂ production irrespective of antigenic cultivation conditions. Simultaneously, PGE₂ synthesis correlated with indexes of MSC‐mediated suppression of mitogen‐ and myelin‐stimulated T cell proliferation in patients with MS. No significant differences in PGE₂ production by autologous and allogeneic MSC have been established. These results have demonstrated that in patients with MS, PGE₂ is one of the possible factors of MSC immunosuppression. The interrelation between PGE₂ concentrations and T cell proliferation suppression mediated by MSC may explain one of the immune mechanisms of cell therapy, which is crucial for the further proper use of MSC in MS research and pathogenic treatment.     

Positive feedback effect of PGE2 on cyclooxygenase-2 expression is mediated by inhibition of Akt phosphorylation in human follicular dendritic cell-like cells

Prostaglandins (PGs) are bioactive lipid mediators generated from the phospholipids of cell membrane in response to various inflammatory signals. To understand the potential role of PGs in PG production itself during immune inflammatory responses, we examined the effect of PGE₂, PGF_2α, and beraprost on COX-2 expression using follicular dendritic cell (FDC)-like HK cells isolated from human tonsils. Those three PGs specifically augmented COX-2 protein expression in a dose-dependent manner after 4 or 8 h of treatment. The enhancing effect was also reflected in the actual production of PGs and the viable cell recovery of germinal center B-cells. To investigate the underlying molecular mechanism, we examined the impact of PI3K inhibitors on PG-induced COX-2 expression. Interestingly, COX-2 induction by PGE₂ and beraprost, but not PGF_2α, was enhanced by wortmannin and LY294002. In line with this result, Akt phosphorylation was inhibited by PGE₂ and beraprost but not by PGF_2α. The distinct effect of PGE₂ and beraprost from PGF_2α was reproduced in Akt-knockdowned HK cells. Our current findings imply that PGE₂ and PGI₂ stimulate COX-2 expression in FDC by inhibiting Akt phosphorylation. Additional studies are warranted to determine the potential role of Akt as a therapeutic target in patients with inflammatory disorders.     

Re-establishment of gap junctional intercellular communication (GJIC) between human endometrial carcinomas by prostaglandin E2

Reduced intercellular communication via gap junctions is correlated with carcinogenesis. Gap junctional intercellular communication (GJIC), between normal human endometrial epithelial cells is enhanced when endometrial stromal cells were present in culture. This enhancement of GJIC between normal epithelial cells also occurs when they are cultured in medium conditioned by stromal cells. This observation indicated that a soluble compound (or compounds) produced and secreted by stromal cells mediates GJIC in epithelial cells. Previous studies have shown that endometrial stromal cells release prostaglandin E₂ (PGE₂) and prostaglandin F_2α (PGF_2α) under physiological conditions. When we evaluated the response of normal endometrial epithelial cells to various concentrations of PGE_2, we found enhanced GJIC with 1 nM PGE₂. This is a smaller increase in GJIC than that induced by medium conditioned by stromal cells. When the extracellular concentration of PGE₂ was measured after incubation with stromal cells, it was found to be similar to the concentrations showing maximal GJIC between the normal epithelial cells. When indomethacin was used to inhibit prostaglandin synthesis by stromal cells, GJIC was reduced but not eliminated between normal endometrial epithelial cells. These observations suggest that although PGE₂ secreted by stromal cells is an important mediator of GJIC between the epithelial cells, it is not the sole mediator. Transformed endometrial epithelial cells did not demonstrate GJIC even in the presence of stromal cells. However, we were able to re-establish GJIC in transformed epithelial cells when we added PGE₂ to the cells. Our findings show that PGE₂ may serve as an intercellular mediator between stromal and epithelial cells that regulates GJIC in normal and malignant epithelial cells. This suggests that maintenance of GJIC by preserving or replacing PGE₂ secretion by endometrial stromal cells may have the potential to suppress carcinogenesis in endometrial epithelial cells.     

Localization and characterization of macrophages in murine uterus

Macrophages are known to be present in the murine uterus and are known to be among those cells comprising the uterine decidual response to pregnancy. The extent of macrophage involvement in the decidual response has not been documented, and there are unresolved questions regarding expression of markers normally associated with macrophages on cells within the decidua. Using tissue immunohistology, macrophages were identified in virgin and pregnant murine uteri. A significant increase in macrophage density was noted during all stages of pregnancy. When uteri from virgin and pregnant mice were enzymatically digested, 10% of uterine cells from virgin and 22% from pregnant mice expressed macrophage markers (binding of rabbit antimouse macrophage serum, Fc gamma receptor expression). Double labeling immunofluorescence demonstrated that the two markers were associated with the same cells. Those results were confirmed in "panning" experiments using a monoclonal antimouse macrophage reagent. In cell suspensions from pregnant murine (C3H/HeN) uteri, 50% of cells exhibiting macrophage markers were I-Ak positive, and macrophages accounted for nearly all I-Ak positive cells in uterine cell suspensions. The results of this study demonstrate that the murine decidual response to pregnancy includes an increase in Fc gamma receptor-bearing macrophages and that a relatively high percentage of those macrophages are Ia positive.     

Effects of prostaglandin E1, E2, and F2α on isolated pial arteries of cat

Responses to prostaglandin (PG), E₁, E₂, and F_2α were studied on isolated feline middle cerebral arteries. At resting state PGF_2α produced strong dose-dependent contractions. PGE₂ elicited weak relaxations at low concentrations, followed by powerful contractions at higher doses. PGE₁ had little effect on resting pial vessels. The relative constrictory potency was PGF_2α > PGE₂ > PGE₁. During active tone, induced by administration of either potassium, norepinephrine, or 5-hydroxytryptamine, relaxations induced by PGE₁ were enhanced, whereas PGE₂-induced relaxations were unaffected. PGE₁ induced relaxations were more pronounced when the active tension had been produced by administration of PGF_2α than with either of the vasoactive amines or potassium. This study demonstrates the importance of smooth muscle tone, and by what means this is achieved, when examining the responses of PG's on cerebral blood vessels.     

Prostaglandin production and cellular aging

Prostaglandin (PG) production by human embryo lung fibroblasts (HELF) is stimulated by a number of effectors including angiotensin, thrombin, bradykinin and ascorbic acid. The types of prostaglandins produced are to a degree effector-dependent. For example, angiotensin stimulates mainly PGE₂ synthesis, thrombin stimulates production of both PGE₂ and prostacyclin while bradykinin and ascorbic acid stimulate production of PGE₂, PGF_2α, prostacyclin and thromboxane A₂. Upon senescence in culture, prostacyclin (PGI₂) production by HELF drops dramatically in response to ascorbic or arachidonic acids. An overall drop in prostaglandin synthesis is observed with bradykinin stimulation. Prostaglandin production is also related to senescence in human skin fibroblasts (HSF). These cells produce predominantly PGI₂. Prostacyclin production in response to bradykinin drops in HSF as they are obtained from individuals of increasing chronologic age. Thus our results indicate changes in prostaglandin production upon senescence, a dependency of these changes on the given stimulus and a correlation between in vivo and in culture aging with respect to prostaglandin production.     

Inhibition of artificially induced decidual cell reaction by indomethacin in the mature oophorectomized rat

Prostaglandin F₂α (PGF₂α) is capable of inducing a decidual cell reaction (DCR) in the hormonally prepared rat. In the present work indomethacin, a PG synthetase inhibitor, was used to determine whether PGF₂α is involved in the DCR induced by artificial stimulation of the endometrium. Thirty-seven animals were oophorectomized and subsequently given daily injections of progesterone for 6 days and one injection of estradiol 17 β on the fourth day. Later on the fourth day, one of several experimental maneuvers was carried out on the right uterine horn of each animal; these included: 1) introduction of phosphatebuffered saline (PBS) twice into the uterus, 2) intrauterine injection of PGF₂α with no subsequent application or manipulation, 3) intrauterine injection of indomethacin followed by subsequent injection of PGF₂α, 4) intrauterine injection of indomethacin with subsequent artificial stimulation (scratch), 5) intrauterine injection of PBS with subsequent scratch, 6) scratch followed by injection of PBS, and 7) scratch followed by a second scratch. The extent of the ensuing DCR was assessed 48 h later by measurement of horn weight, by light and electron microscopy, by ranking the DCR, and by the mitotic index. Indomethacin significantly reduced the horn weight in animals treated with scratch but had a much less marked effect on animals treated with PGF₂α. Similarly the rank of the DCR and the mitotic index were significantly less in endometria treated by indomethacin with scratch than those treated by indomethacin with PGF₂α. From these findings it was concluded that the DCR induced by scratch was inhibited, but not abolished, when preceded by indomethacin. Conversely the DCR induced by PGF₂α was not inhibited by indomethacin, thus demonstrating that when local generation of PG is reduced or abolished, PGF₂α can sustain the decidual cell response.     

Umbilical cord tissue-derived mesenchymal stem cells grow best under GMP-compliant culture conditions and maintain their phenotypic and functional properties

Mesenchymal stem cells (MSCs) are fibroblast-like multipotent stem cells that can differentiate into cell types of mesenchymal origin. Because of their immune properties and differentiation, potential MSCs are discussed for the use in tissue regeneration and tolerance induction in transplant medicine. This cell type can easily be obtained from the umbilical cord tissue (UCMSC) without medical intervention. Standard culture conditions include fetal bovine serum (FBS) which may not be approved for clinical settings. Here, we analyzed the phenotypic and functional properties of UCMSC under xeno-free (XF, containing GMP-certified human serum) and serum-free (SF) culture conditions in comparison with standard UCMSC cultures. Phenotypically, UCMSC showed no differences in the expression of mesenchymal markers or differentiation capacity. Functionally, XF and SF-cultured UCMSC have comparable adipogenic, osteogenic, and endothelial differentiation potential. Interestingly, the UCMSC-mediated suppression of T cell proliferation in an allogeneic mixed lymphocyte reaction (MLR) is more effective in XF and SF media than in standard FBS-containing cultures. Regarding the mechanism of action of MLR suppression, transwell experiments revealed that in neither UCMSC culture a direct cell-cell contact is necessary for inhibiting T cell proliferation, and that the major effector molecule is prostaglandin E₂ (PGE₂). Taken together, GMP-compliant growth media qualify for long-term cultures of UCMSC which is important for a future clinical study design in regenerative and transplant medicine.     

Influence of prostaglandins and a prostaglandin H synthase inhibitor on cervical secretion of the guinea-pig

The modulatory effects of several prostaglandins and a prostaglandin H synthase inhibitor (indomethacin) on basal as well as nerve stimulation induced secretion from the cervical glands of the guinea-pig were studied. Hypogastric nerve stimulation resulted in a secretory response of + 113%. Indomethacin dose dependently inhibited this secretory response. Prostaglandins E₂, F_2α and I₂ inhibited and 19-OH prostaglandin E₁ reduced nerve stimulation induced secretion. Prostaglandin I₂ and 19-OH PGE₁ markedly enhanced basal secretion, while indomethacin as well as PGE₂ and PGF_2α did not induce any secretion of cervical glands. However, PGF_2α in combination with the α-adrenergic blocker phentolamine resulted in an increase in secretion. The inhibitory effect of prostaglandins on cholinergic secretory innervation might be due to stimulation of adrenergic nerves exerting an inhibitory influence on cholinergic secretomotor innervation. It is suggested that PGI₂ and 19-OH PGE₁ exert postjunctional stimulatory effects on the secretory lining and that a lack of secretory effect of PGF_2α at least in part may be due to stimulatory effects on adrenergic neurons, inhibiting cholinergic secretomotor transmission. Thus, in this in vitro study it is shown that metabolites of the arachidonic acid cascade and a prostaglandin H synthase inhibitor can modulate cervical secretion and thus maybe influence fertilization.