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Biomedical subjects

R W Kelly

Publications and source records attributed to R W Kelly.

At least 19 recordsLinked to original sources
PubMed2006

Expression of natural antimicrobials by human placenta and fetal membranes.

Preterm birth associated with infection is a major clinical problem. We hypothesized that this condition is associated with altered expression of natural antimicrobial molecules (beta-defensins (HBD), elafin). Therefore, we examined expression of these molecules and their regulation by proinflammatory cytokines in placentae and fetal membranes from term pregnancy. HBD1-3 and elafin were localized by immunohistochemistry in fetal membranes and placenta. Real-time quantitative PCR was used to examine mRNA expression in primary trophoblast cells treated with inflammatory molecules. HBD1-3 and elafin were immunolocalized to placental and chorion trophoblast layers of fetal membranes and placenta. Immunoreactivity was also observed in amnion epithelium and decidua. No differences were noted between samples from women who were not in labour compared to those in active labour. In in vitro cultures of primary trophoblast cells, HBD2 and elafin mRNA expression was upregulated by the proinflammatory cytokine, IL-1beta. These results suggest that the chorion and placental trophoblast layers may be key barriers to the progression of infection in the pregnant uterus. Natural antimicrobial expression may be altered in response to inflammatory mediator expression associated with the onset of labour and/or uterine infection, providing increased protection when the uterus may be particularly susceptible to infection.

Anti-Infective Agents↗
PubMed2006

Identification of eggshell membrane proteins and purification of ovotransferrin and beta-NAGase from hen egg white.

Exposure of selected Gram-positive and Gram-negative bacterial pathogens to egg shell membranes (ESM) significantly reduced their thermal resistance and/or inactivated cells. Although the components responsible for this antibacterial activity have not been conclusively identified, several proteins associated with the ESM activity have been identified including beta-N-acetylglucosaminidase, lysozyme and ovotransferrin, with each displaying varying degrees of antibacterial activity. Numerous attempts to purify active fractions of beta-N-acetylglucosaminidase, lysozyme and ovotransferrin from the ESM proved somewhat limited; however, hen egg white (HEW) beta-N-acetylglucosaminidase was purified using a two-step chromatographic procedure, isoelectric focusing followed by cation exchange chromatography. Pure fractions of ovotransferrin were also obtained in the process. SDS-PAGE electrophoresis and Matrix-Assisted Laser Desorption Time-of-Flight Mass Spectrometry were then used to partially characterize the individual protein components. Purified protein fractions such as these will be required in order to fully elucidate the mechanism responsible for the antimicrobial properties associated with the ESM.

Acetylglucosaminidase↗
PubMed2005

Gastric epithelial anti-microbial peptides--histological correlation and influence of anatomical site and peptic ulcer disease.

BACKGROUND AND AIMS: Natural anti-microbial peptides are increasingly recognised for their protective effects in mucosal surfaces. We, therefore, aimed at investigating their expression in the human stomach in a range of peptic conditions. METHODS: We assessed the expression of epithelial secretory leukocyte protease inhibitor, human beta-defensins (HBD1 and HBD2), and alpha-defensin (HD5) in gastric biopsies taken from 52 patients, median age of 55 years. Expression of peptide mRNA was determined using real-time quantitative polymerase chain reaction. The activity of gastritis was graded on a 0-3 scale. RESULTS: The antrum had a median secretory leukocyte protease inhibitor of 0.93 and HBD1 of 0.42, compared with 0.13 (P = 0.001) and 0.08 units (P = 0.002) respectively in the gastric body. The antral histological scores correlated positively with HBD2 expression (r = 0.69; P< 0.001) and negatively with HBD1 (r = -0.47; P = 0.006) particularly in the absence of aspirin. Patients with Helicobacter pylori gastritis, gastric or duodenal ulcers had lower expression of HBD1 and greater expression of HBD2 than in controls. The intake of aspirin by patients infected with H. pylori was associated with marked rise in the expression of HD5 and less expression of secretory leukocyte protease inhibitor. CONCLUSIONS: Gastric epithelial anti-microbial peptides are influenced by anatomical site, grade of gastritis, peptic ulceration, and can be modulated by aspirin.

Adolescent↗
PubMed2003

Urinalysis for interleukin-8 in the non-invasive diagnosis of acute and chronic inflammatory diseases.

BACKGROUND AND AIMS: Given its role in mediating inflammation, the use of urinary interleukin-8 (IL-8) was assessed in the non-invasive diagnosis of acute and chronic inflammatory diseases. METHODS: IL-8 was measured by an enzyme linked immunosorbent assay in random urine samples (1 ml each) carrying code numbers and taken from 208 patients: 177 adults and 31 children presenting with a range of active or inactive inflammatory conditions. RESULTS: In the appropriate controls and in patients with inactive inflammation, the median urinary IL-8 levels ranged from 7-12 pg/ml, compared with 104 pg/ml in active ulcerative colitis (p = 0.002), 54 in active Crohn's disease (p = 0.025), 93 in active rheumatoid arthritis (p = 0.001), 107 in acute cholecystitis (p<0.0001), 127 in acute appendicitis (p = 0.0001), and 548 pg/ml in urinary tract infection (p<0.0001). Children with non-viral inflammation/infection also had higher IL-8 values (median, 199 pg/ml; p = 0.0001) than those with viral infection (median, 7 pg/ml) or non-specific conditions (median, 10 pg/ml). In the study group as a whole urinary IL-8 values correlated positively with peripheral blood white cell count (r = 0.32; p < 0.001), erythrocyte sedimentation rate (r = 0.41; p<0.001), and C-reactive protein (r = 0.33; p<0.001). CONCLUSION: Taking the appropriate clinical situation into account, urinary IL-8 measurement helps in the non-invasive assessment of active inflammation in at least a number of common acute and chronic conditions.

Acute Disease↗
PubMed2002

Administration of an antiprogesterone up-regulates estrogen receptors in the endometrium of women using Norplant: a pilot study.

OBJECTIVE: To determine the effect of a single dose of mifepristone (200 mg) on endometrial estrogen and progesterone receptors in Norplant users. DESIGN: A prospective single-blind placebo-controlled pilot study. SETTING; Women were recruited from a large family planning clinic and were studied either at the clinic or in a clinical research unit attached to a teaching hospital gynecology department. PATIENT(S): Eight women using Norplant and experiencing vaginal bleeding more often than once every 24 days. All completed the study. INTERVENTION(S): Endometrial biopsies were taken after treatment with both placebo and 200 mg of mifepristone, both given at the start of a bleeding episode. MAIN OUTCOME MEASURE(S): Expression of endometrial progesterone (PR) and estrogen (ER) receptors, ovulation, and vaginal bleeding. RESULT(S): Mifepristone administration was associated with down-regulation of PR receptor subtype B and up-regulation of ER. Women treated with mifepristone showed a tendency to increased ovulation rates and reduced vaginal bleeding. CONCLUSION(S): The effect of mifepristone on endometrial steroid receptors was consistent with functional inhibition of progesterone. The findings warrant further investigation of this regimen as a strategy to reduce frequent bleeding.

Biopsy↗
PubMed2002

Autocrine/paracrine regulation of apoptosis in epithelial cells by prostaglandin E2.

This study was designed to investigate the effect of IL-1alpha-induced up-regulation of cyclooxygenase-2 (COX-2) on prostaglandin E(2) (PGE(2)) secretion and the subsequent phenotypic effects of PGE(2) on epithelial cells. The effect of IL-1alpha on COX-2 expression was investigated in the T24 bladder epithelial cell line following treatment with 0, 0.05, 0.5, 1 or 10 ng/ml IL-1alpha for 1, 2, 4 or 6 h. Quantitative PCR confirmed up-regulation of expression of COX-2 with maximal expression observed following treatment with 0.5 ng/ml IL-1alpha for 1 h. Co-treatment of the cells with 0.5 ng/ml IL-1alpha in the presence or absence of 100 ng/ml IL-1 receptor antagonist (RA) abolished the up-regulation in COX-2 expression confirming that the effect of IL-1alpha is mediated via its membrane-bound receptors. Treatment with 0.5 ng/ml IL-1alpha resulted in a time-dependent increase in PGE(2) secretion with maximal secretion detected at 24 and 48 h after stimulation with IL-1alpha. Co-treatment of the cells with IL-1alpha and IL-1RA or the COX-2 enzyme inhibitor NS398 abolished the IL-1alpha mediated secretion of PGE(2). Treatment of T24 cells with 100 nM PGE(2) resulted in a significant elevation in cAMP generation confirming the expression of functional PGE(2) receptors. Finally, the effect of exogenous treatment with PGE(2) on apoptosis of T24 cells was assessed using cell death detection ELISA. T24 cells were treated with camptothecin to induce apoptosis in the presence or absence of 50 or 100 nM PGE(2) or 10 microM forskolin. Treatment of T24 cells with increasing doses of camptothecin alone resulted in a significant increase in the induction of apoptosis (P<0.01). However, co-treatment of the cells with 50 or 100 nM PGE(2) or 10 microM forskolin resulted in the inhibition of induction of the apoptotic pathway by camptothecin. These data demonstrate that PGE(2) inhibits apoptosis of epithelial cells possibly via cAMP-dependent pathway.

Apoptosis↗
PubMed2001

Regulation of prostaglandin availability in human fetal lung by differential localisation of prostaglandin H synthase-1 and prostaglandin dehydrogenase.

Specialisation of the respiratory portion of human fetal lung commences around 20-24 weeks gestation. In contrast, human fetal lung in vitro has the capacity to self-differentiate from 12 weeks gestation when grown in media devoid of growth factors or hormones, suggesting activation of autocrine or paracrine factors in vitro, or removal of the fetus from in utero inhibitory mechanisms. Prostaglandins play a key role during in vitro human fetal lung development and are synthesised by prostaglandin H synthase-1 (PGHS-1) and inactivated by 15-hydroxyprostaglandin dehydrogenase (PGDH) with formation of inactive 13,14-dihydro-15-keto-prostaglandins. We have used quantitative immunohistochemistry to determine expression and localisation of PGHS-1, PGDH, PGE2 and 13,14-dihydro-15-keto-PGE2 (PGEM) in human fetal lung with in situ hybridisation to localise PGHS-1 and PGDH mRNA. For the catabolic enzyme PGDH, amounts of mRNA, protein and enzyme product PGEM are increased within epithelium of distal as compared to more proximal airways. For PGHS-1, comparable amounts of mRNA, protein and enzyme product PGE2 are found in proximal and distal lung epithelium. Catabolism by PGDH is a sensitive mechanism for regulating bioavailability of prostaglandins and we propose that active catabolism of prostaglandins within human fetal lung epithelium is an inhibitory mechanism retarding epithelial differentiation in utero.

Cyclooxygenase 1↗
PubMed2001

Fibroblast heterogeneity: existence of functionally distinct Thy 1(+) and Thy 1(-) human female reproductive tract fibroblasts.

Little is known about fibroblasts from the female reproductive tract, much less whether or not functional subsets exist. Fibroblasts are key as sentinel cells for recruiting white blood cells and for wound healing. The purpose of this research was to evaluate the possibility that functional subsets of fibroblasts exist in the human female reproductive tract. The strategy used was to define fibroblast subpopulations based on their surface expression of the Thy 1 antigen. In situ staining of human myometrium and endometrium showed heterogeneous staining for Thy 1. Freshly derived strains of fibroblasts from the myometrium and endometrium also demonstrated heterogeneous Thy 1 expression. For the first time, using magnetic beading and fluorescence-activated cell sorting, human myometrial fibroblasts were successfully separated into functionally unique Thy 1(+) and Thy 1(-) subsets. Both subsets produced the proinflammatory cytokines interleukin (IL)-6 and IL-8 after IL-1beta stimulation, but only the Thy 1(+) subset produced MCP-1. Furthermore, only Thy 1(+) fibroblasts up-regulated CD40 surface expression with IL-1beta or interferon-gamma treatment. Engagement of CD40 in the Thy 1(+) subpopulation induced IL-6, IL-8, and MCP-1. The discovery of functional subsets of reproductive tract fibroblasts now permits assessment of their roles in the normal functions of the reproductive tract and in disease states such as adhesions and menorrhagia.

CD40 Antigens↗
PubMed2001

The endocrinology of menstruation--a role for the immune system.

The human endometrium displays characteristic features, both structural and functional, across the menstrual cycle. It is the sex steroid hormones, oestrogen and progesterone, that drive the endometrium through the different phases of the cycle. Oestrogen and progesterone act sequentially to regulate cellular concentrations of their respective receptors, this interaction initiates gene transcription. Thereafter a cascade of local events prepares the endometrium for implantation, but in the absence of pregnancy, progesterone withdrawal leads to menstruation and cyclic repair. Withdrawal of progesterone from an oestrogen-progesterone primed endometrium is the initiating event for the cascade of molecular and cellular interactions that result in menstruation. Progesterone withdrawal first affects cells with progesterone receptors. Early events in the menstrual process are vasoconstriction and cytokine up-regulation. The activation of lytic mechanisms is a later event and involves cells that may lack progesterone receptors, for example, uterine leucocytes and epithelial cells. Hence progesterone withdrawal results in a local increase of inflammatory mediators and the enzymes responsible for tissue breakdown. The total complex of local factors implicated in normal menstrual and aberrant menstrual bleeding are yet to be fully defined.

Adult↗
PubMed2001

The NF-kappaB pathway in human endometrium and first trimester decidua.

Nuclear factor kappa B (NF-kappaB) regulates proinflammatory genes and may be involved in inflammation associated with reproductive events e.g. menstruation, implantation. Activation of NF-kappaB involves several protein kinases and subsequent degradation of an endogenous inhibitor, IkappaBalpha. This study details expression of NF-kappaB pathway intermediates in human endometrium and first trimester decidua. Messenger RNA was detected for IkappaBalpha, and IkappaB kinase gamma (IKKgamma, a scaffolding protein) and the protein kinases, IKKalpha, IKKbeta, NF-kappaB inducing kinase (NIK), mitogen-activated protein kinase Erk kinase kinase 1 (MEKK1) and TANK-binding kinase 1 (TBK1) using real-time quantitative polymerase chain reaction (PCR). IkappaBalpha and TBK1 mRNA were increased in the perimenstrual phase of the menstrual cycle. This suggests that there is activation of NF-kappaB due to premenstrual progesterone withdrawal, since NF-kappaB activity increases IkappaBalpha gene expression. Differential expression of NF-kappaB pathway intermediates occurred when progesterone concentrations increased in early pregnancy; IKKalpha and NIK mRNA levels increased in decidua whilst IKKbeta and MEKK1 mRNA levels declined. Expression profiles of IKKalpha and NIK proteins were determined immunohistochemically. Both were detected in glandular epithelium and endothelium of endometrium. In decidua, both were present in epithelium and decidualized stromal cells. The results of this study suggest that NF-kappaB is activated during menstruation. During early pregnancy, NF-kappaB may also be activated (via IKKalpha-NIK) and may regulate the expression of molecules vital for implantation and successful pregnancy. However, pro-inflammatory signalling to NF-kappaB (via IKKbeta-MEKK1) may be down-regulated in early pregnancy, contributing to the immunosuppressive mechanisms which prevail at this time.

Base Sequence↗
PubMed2001

Cd40 expression in uterine tissues: a key regulator of cytokine expression by fibroblasts.

CD40 is a cell surface receptor initially discovered on cells of the hemopoietic lineage. Its primary role on immune cells is to enhance their activation and hence their production of cytokines and immunomodulatory molecules. Recently, CD40 has also been detected on human fibroblasts. An emerging view of the fibroblast is that it is far more than a structural cell, being capable of intimate interaction with cells of the immune system. In fibroblasts from several tissues, the engagement of CD40 with its ligand (CD40L) resulted in the secretion of proinflammatory molecules such as interleukin-6 (IL-6) and IL-8. Currently, there are few data about the presence of the CD40-CD40L system in female reproductive tissues. This study investigates the expression of CD40 by human endometrium, myometrium, and cervix both in situ and in tissue explant-derived fibroblasts. CD40 was detected mainly in the perivascular region of endometrium, myometrium, and cervix. Light staining for CD40 was observed in stromal elements. Additionally, the basal epithelium of cervix expressed CD40. Fibroblastic cells derived from all three sources express low levels of CD40, and this is up-regulated with interferon-gamma treatment (500 U/mL; 72 h). When activated with interferon-gamma and CD40L, the fibroblasts secreted increased amounts of IL-6, IL-8, and MCP-1. These data suggest that the CD40-CD40L system may provide a link between the resident structural cells of these reproductive tissues and the infiltrating immune cells or activated platelets that may express CD40L. The possible interaction of CD40 with CD40L may be particularly important during events such as menstruation and cervical ripening, where up-regulation of the proinflammatory molecules IL-6 and IL-8 is viewed as critical for these processes. In addition, dysregulation of this system may be a contributory factor to problems such as menstrual dysfunction and preterm labor.

CD40 Antigens↗
PubMed2001

Cytokine control in human endometrium.

Cytokines within endometrium participate in both menstruation and implantation but also contribute to the defence mechanisms of the mucosal epithelium. Endometrium is under the control of steroid hormones, particularly progesterone and, thus, control of cytokines by this steroid is important. Although appreciable numbers of progesterone receptors are not found in endometrial leucocytes, progesterone can modulate cytokines by acting on uterine cells expressing the receptor. The NFkappaB pathway is important in the control of cytokine synthesis and can modulate production of chemokines, matrix metalloproteinases and the inducible prostaglandin synthesis enzyme COX-2. NFkappaB activity can be inhibited by progesterone by either stimulating synthesis of IkappaB, the molecule that restrains NFkappaB in the cytosol, or after binding to the nuclear receptor, competing with NFkappaB for recognition sites on the relevant gene. In this way, progesterone can limit pro-inflammatory pathways. The major palliatives for endometrial dysfunctions such as menorrhagia and dysmenorrhoea have been the non-steroidal anti-inflammatory drugs that inhibit prostaglandin synthesis. Prostaglandins have major effects on cytokine production but the direct action of prostaglandin E on leucocytes is not a pro-inflammatory response but is to stimulate interleukin 10 and inhibit interleukin 12 synthesis. The likely effect of the non-steroidal anti-inflammatory drugs is on the cells surrounding the small blood vessels, where a synergistic action between prostaglandin and chemokine will induce leucocyte entry and activation leading to lysis of connective tissue and menstruation. At the time of implantation, tight control of cytokine synthesis is required. Although leukaemia inhibitory factor is essential to implantation, the mouse knockout models show that the prostaglandin system is also essential but that there are mutually supportive pathways that compensate for the knockout of many cytokines.

Animals↗
PubMed2000

Transfer and metabolism of prostaglandin E(2)in the dual perfused human placenta.

Prostaglandins (PGs) are potent paracrine hormones that are important for the control of several functions in the uterus and fetus during pregnancy and parturition. PGs are rapidly metabolized to inactive metabolites by prostaglandin dehydrogenase (PGDH). However, the regulation of transfer and metabolism of PGs across the placenta is not well understood. This study used an in vitro dual perfused human placental cotyledon preparation to examine the production of the potent vasoactive and myometrial stimulants PGE(2)and PGF(2alpha), transfer of PGs from the maternal to the fetal circulation and the metabolism of PGs by PGDH. Secretion of PGE(2)was greater into the fetal compared to the maternal circulation. PGE(2)output was higher than PGF(2alpha)and concentrations of PGE(2)and PGF(2alpha)metabolites (PGEM and PGFM) were greater in both fetal and maternal outputs when compared to the primary prostaglandins. Infusion of PGE(2)into the maternal circulation did not result in increased PGE(2)efflux but PGEM was output was increased, demonstrating a rapid and efficient metabolism by the placenta. There was no significant transfer of PGE(2)across to the fetal circulation, although there was some transfer but in the form of inactivated PGEM. There was no significant interconversion of PGE(2)to PGF(2alpha)by the 9-keto-reductase pathway. Expression of PGDH as detected by immunoblot was high in placenta. This PGDH was localized throughout the syncytiotrophoblast at the fetal-maternal interface and also in extravillous trophoblast cells. The presence of PGDH at this site acts to stabilize output of primary PG from the placenta and also as a barrier preventing transfer to the fetal circulation, resulting in the separation of PG homeostasis in the fetus and mother.

Biological Transport, Active↗
PubMed2000

Presence of secretory leukocyte protease inhibitor in human endometrium and first trimester decidua suggests an antibacterial protective role.

Secretory leukocyte protease inhibitor (SLPI) is a neutrophil elastase inhibitor which also has antibacterial and anti-inflammatory properties. It is found associated with mucosal membranes. Although SLPI has been reported in the cervix it has not thus far been reported in human endometrium. This study investigates the presence of SLPI in endometrium, first trimester decidua and trophoblast. Cultured first trimester decidua was found to produce 4. 7 +/- 2.0 ng/mg/24 h of SLPI. Endometrium and trophoblast were both found to secrete significantly lower amounts of SLPI (P < 0.01) although endometrial expression was menstrual cycle dependent with increased secretion in the secretory phase. Although relatively low concentrations of SLPI were released from the endometrium during culture, most of the SLPI remained associated with the tissue and could be recovered with mild acid extraction. This is in agreement with the high isoelectric point (pI) for SLPI, associated with high solubility at low pH. The main site of SLPI synthesis in endometrium and decidua was found to be the glandular epithelium. An antibiotic role for SLPI in the endometrium and decidua during implantation and pregnancy would be consistent with the expression profile and localization of SLPI.

Amino Acid Sequence↗
PubMed2000

The effect of mifepristone administration on leukocyte populations, matrix metalloproteinases and inflammatory mediators in the first trimester cervix.

Cervical ripening is analogous to an inflammatory reaction characterized by an influx of inflammatory cells and an increase in inflammatory mediators. The anti-gestogen mifepristone is highly effective in inducing cervical ripening in women throughout gestation. However, its mechanism of action is largely unknown. The aim of the study was to investigate the effect of in-vivo administration of mifepristone on inflammatory cells and mediators in the cervix. Cervical biopsies were taken from women undergoing a first trimester termination of pregnancy at 0, 6, 12, 24 and 36 h (n = 6 per group) after mifepristone administration. Biopsies were fixed for immunohistochemistry and also cultured for subsequent analysis of culture media by radioimmunoassay or enzyme-linked immunosorbent assay. After administration of mifepristone (6-24 h), there was an increase in immunostaining for leukocyte common antigen (CD45), neutrophil elastase, monocytes (CD68), and matrix metalloproteinases (MMP)-1, -8 and -9. Immunostaining for MMP-2 and tissue inhibitor of metalloproteinases (TIMP)-1, -2 and -4 were unaffected by mifepristone treatment. Secretion of monocyte chemotactic protein (MCP-1) was significantly (P < 0.05) increased from biopsies taken 6-24 h after mifepristone administration. Cervical biopsies also released interleukin-8 (IL-8), prostaglandin (PG) E(2), PGF(2alpha) and prostaglandin metabolites (PGEM and PGFM) although their secretion was unaffected by mifepristone treatment. This study suggests that mifepristone may, in part, effect cervical ripening by modulating the influx of inflammatory cells into the cervix, up-regulating MMP expression and inducing chemokine secretion by cervical tissue.

Abortifacient Agents, Steroidal↗
PubMed2000

Increase in 15-hydroxyprostaglandin dehydrogenase activity in the ovine placentome at parturition and effect of oestrogen.

Type 1 NAD(+)-dependent 15-hydroxyprostaglandin dehydrogenase (PGDH) is the key enzyme for metabolism of active primary prostaglandins to inactive forms in gestational tissues. The present study examined the activity and immunolocalization of PGDH in the ovine placenta, fetal membranes and uterus over the latter half of pregnancy, and its potential regulation by oestradiol. Placenta, fetal membranes and myometrium were collected from sheep with known single insemination dates on days 70, 100 and 135 of gestation and in active labour demonstrated by electromyographic activity. In addition, chronically catheterized fetuses were infused with oestradiol (100 microgram kg(-1) per 24 h) (n = 5) or saline vehicle into the fetus from day 120 to day 125. PGDH activity measured in placental extracts remained constant from day 70 to day 135 of gestation, and then significantly (P < 0.05) increased by 300% in active labour. Immunoreactive PGDH was localized in the placentome at all stages and was present predominantly in the fetal component of the placentome in uninucleate, but not in binucleate, trophoblast cells. Similarly, in the fetal membranes PGDH immuno-reactivity was present in the uninucleate trophoblast but not in the binucleate cells of the chorion. PGDH immunostaining was also present in the endometrial luminal epithelium, in the smooth muscle of the myometrium, and the glandular epithelium of the cervix. Infusion of oestradiol into the fetal circulation from day 120 to day 125 of gestation had no effect on placental PGDH activity. Immunohistochemistry was used to localize oestrogen receptor alpha in intrauterine tissues to investigate further the failure of oestradiol to increase PGDH activity. Immunoreactive oestrogen receptor alpha was not present in the fetal component of the placenta, although it was expressed in adjacent maternal-derived cells. It is concluded that (1) PGDH activity increases in late gestation; (2) PGDH is expressed in uninucleate trophoblast cells in the ovine placenta and fetal membranes, and also in the maternal endometrial epithelium and stroma, myometrium and cervix; (3) oestrogen receptor alpha is not expressed in fetal cells in the placenta or fetal membranes; and (4) the increase in PGDH activity is not regulated by oestradiol administered to the fetus.

Animals↗
PubMed1999

The action of prostaglandin E2 on the human cervix: stimulation of interleukin 8 and inhibition of secretory leukocyte protease inhibitor.

OBJECTIVE: The objective of this study was to investigate regulation of inflammatory mediators implicated in cervical ripening and to explore the mechanisms by which the clinically effective agent prostaglandin E2 may mediate cervical ripening. STUDY DESIGN: Cervical biopsy specimens were taken from healthy, nonpregnant women undergoing a hysterectomy for a benign nonmalignant condition and were cultured, with treatments in quadruplicate, for 24 hours in media supplemented with progesterone, dexamethasone, nitric oxide, interleukin 8, and prostaglandin E2. Media were collected and assayed by enzyme-linked immunosorbent assay for interleukin 8, secretory leukocyte protease inhibitor, and prostaglandin E2. Ethical approval was obtained for this study from the local ethics committee. RESULTS: Interleukin 8 release from cervical explants was stimulated by prostaglandin E2 and nitric oxide and inhibited by progesterone and dexamethasone. Secretory leukocyte protease inhibitor release from cervical explants was stimulated by progesterone and inhibited by prostaglandin E2. Prostaglandin E2 release from cervical explants was stimulated by nitric oxide. CONCLUSION: Complex interactions occur between inflammatory cytokines within the cervix; these results further our understanding of the mechanism of cervical ripening.

Adult↗