scholarly journals Expression of cyclo-oxygenase types-1 and -2 in human fetal membranes throughout pregnancy

1999 ◽  
Vol 22 (2) ◽  
pp. 125-130 ◽  
Author(s):  
D Slater ◽  
W Dennes ◽  
R Sawdy ◽  
V Allport ◽  
P Bennett
Keyword(s):  
Mrna Expression ◽  
Gestational Age ◽  
Prostaglandin Synthesis ◽  
Fetal Membranes ◽  
Activity Levels ◽  
Third Trimester ◽  
Human Amnion ◽  
Human Labour ◽  
Cox 2 ◽  
Cox 1

Human labour is associated with increased prostaglandin synthesis within the fetal membranes. We have studied the expression of the two isoforms of the central prostaglandin synthetic enzyme, cyclo-oxygenase (COX-1 and COX-2), in human fetal membranes throughout pregnancy, at mRNA, protein and activity levels. COX-1 mRNA expression was low in human amnion and chorion-decidua and did not change with gestational age. COX-2 mRNA expression in fetal membranes increased with gestational age, with significant up-regulation prior to the onset of labour and in association with labour. Protein concentrations of COX-1 did not change, whilst concentrations of COX-2 increased from the first to the third trimester. COX activity increased with gestational age and in association with labour, although prostaglandin production in fetal membranes collected after labour was reduced, suggesting reduced substrate supply. These data suggest that it is up-regulation of COX-2, rather than of COX-1, which mediates increased prostaglandin synthesis within the fetal membranes at term. Much of the increase in COX-2 expression precedes the onset of labour, suggesting that it is a cause, rather than a consequence, of labour.

Expression of adrenomedullin mRNA is altered with gestation and labour in human placenta and fetal membranes

2006 ◽  
Vol 110 (3) ◽  
pp. 337-342 ◽  
Author(s):  
Alfia Al-Ghafra ◽  
Shaun P. Brennecke ◽  
Roger G. King ◽  
Neil M. Gude
Keyword(s):  
Mrna Expression ◽  
Relative Abundance ◽  
Gestational Age ◽  
Northern Blot Analysis ◽  
Fetal Membrane ◽  
Fetal Membranes ◽  
Tissue Extracts ◽  
Human Labour ◽  
Positive Correlations ◽  
Labour Group

The aim of the present study was to investigate whether placental and fetal membrane AdM (adrenomedullin) mRNA expression changes with gestation and human labour, as we have previously found labour-associated changes in AdM content in fetal membranes [Al-Ghafra, Gude, Brennecke and King (2003) Clin. Sci. 105, 419–423]. Placentas and fetal membranes were collected either at term or pre-term from women either in-labour or not-in-labour, and AdM mRNA abundance was measured in tissue extracts by Northern blot analysis. Increases were found in the relative abundance of amniotic tissue AdM mRNA in both in-labour and not-in-labour groups at term compared with those at pre-term, and there were positive correlations with gestational age. Relative abundance of choriodecidual tissue AdM mRNA was also significantly elevated in the not-in-labour groups between pre-term and term tissues, although there was no significant correlation with gestational age. However, placental AdM mRNA expression was neither significantly increased at term (compared with pre-term) nor correlated with gestational age. In addition, there were significant increases in AdM mRNA in amnion and choriodecidua in the in-labour group compared with the not-in-labour group for both pre-term and term gestations. There was no difference in AdM mRNA in placental tissues between labour groups. In conclusion, the present study provides evidence that AdM production by fetal membranes is increased in amniotic and choriodecidual tissues at term, compared with pre-term, and in response to labour.

scholarly journals Differential expression of cyclooxygenase 1 and cyclooxygenase 2 in the bovine oviduct

2006 ◽  
Vol 191 (1) ◽  
pp. 263-274 ◽  
Author(s):  
Simone Odau ◽  
Christoph Gabler ◽  
Christoph Holder ◽  
Ralf Einspanier
Keyword(s):  
Mrna Expression ◽  
Estrous Cycle ◽  
Luteal Phase ◽  
Cellular Level ◽  
Differential Distribution ◽  
Cyclooxygenase 1 ◽  
Epithelial Cell Layer ◽  
Cox 2 ◽  
Cycle Dependent ◽  
Cox 1

The aim of the present study was to investigate the enzymes for the local prostaglandin (PG) biosynthesis present in the bovine oviduct during the estrous cycle to influence early reproductive events. Bovine oviducts were classified into four phases: pre-ovulatory, post-ovulatory, early-to-mid luteal, and late luteal phase, subdivided further into ipsi- or contralateral site and separated into ampulla or isthmus. Oviductal cells were gained by flushing the oviductal regions. Quantitative real-time reverse transcriptase-PCR was performed for the secretory and cytosolic phospholipases A2 (sPLA2IB, cPLA2α, and cPLA2β) and cyclooxygenases (COX-1 and COX-2) as the first step enzymes of PG synthesis. COX-1 and cPLA2β showed significant highest mRNA expression around and before ovulation compared with the luteal phase respectively. sPLA2IB and cPLA2α mRNA expression was unregulated during the estrous cycle. Regional differences in mRNA content were found for sPLA2IB with higher mRNA expression in the ampulla than in the isthmus. Western blot analysis revealed the highest COX-1 protein content in the early-to-mid luteal phase. Immunohistochemistry demonstrated that COX-1 was localized in epithelial and smooth muscle cells, whereas COX-2 was only localized in epithelial cells. COX-2 showed a differential distribution within the epithelial cell layer suggesting a regulation on a cellular level, although the COX-2 mRNA and protein amounts did not vary throughout the estrous cycle. A COX activity assay of oviductal cells revealed that COX activity originated predominantly from COX-1 than from COX-2. Treatment of primary oviductal cells with 10 pg/ml 17β-estradiol or 10 ng/ml progesterone resulted in a higher expression of COX-2 and cPLA2α, but not of the other enzymes. The expression pattern of these enzymes suggests that an estrous-cycle dependent and region-specific PG synthesis in the bovine oviduct may be required for a successful reproduction.

scholarly journals Cross Talk between PKC and CREB in the Induction of COX-2 by PGF2α in Human Amnion Fibroblasts

Endocrinology ◽  
2012 ◽  
Vol 153 (10) ◽  
pp. 4938-4945 ◽  
Author(s):  
C. M. Guo ◽  
N. Kasaraneni ◽  
K. Sun ◽  
L. Myatt
Keyword(s):  
Prostaglandin F2α ◽  
Dominant Negative ◽  
Fetal Membranes ◽  
Camp Response Element ◽  
Human Amnion ◽  
Rate Limiting Step ◽  
Inducible Synthesis ◽  
Fp Receptor ◽  
Cox 2 ◽  
Interfering Rna

Abstract Compelling evidence indicates a crucial role of prostaglandin F2α (PGF2α) in parturition. Both the maternal and fetal sides of the fetal membranes synthesize PGF2α, which exerts effects via the prostaglandin F2α receptor (FP) that is coupled to the activation of protein kinase C (PKC). Cyclooxygenase-2 (COX-2) catalyzes the rate-limiting step of the inducible synthesis of prostaglandin. Although activation of PKC is known to induce COX-2 expression, it is not clear whether PGF2α can induce COX-2 via FP receptor-coupled PKC activation. COX-2 promoter carries a cAMP-response element (CRE) and phosphorylation of CRE binding protein 1 (CREB1) is associated with COX-2 expression in human amnion fibroblasts. We demonstrated that human amnion fibroblasts produced PGF2α and expressed FP receptor. PGF2α increased COX-2 expression and CREB1 phosphorylation, which could be blocked by either the FP receptor antagonist AL8810 or PKC inhibitor Ro31-7549. The PKC activator, phorbol-12-myristate-13-acetate (PMA), could mimic the induction of COX-2 and CREB1 phosphorylation. The induction of COX-2 by PGF2α and PMA could be attenuated by the small interfering RNA-mediated knockdown of CREB1 expression or overexpressing dominant-negative CREB1. A chromatin immunoprecipitation assay showed that the binding of CREB1 to the COX-2 promoter was increased by PGF2α and PMA in amnion fibroblasts. In conclusion, we provide evidence that PGF2α induces COX-2 expression via the FP receptor and phosphorylates CREB1 by PKC, thus increasing CREB1 binding to the COX-2 promoter and the expression of COX-2 in human amnion fibroblasts. This feed-forward loop may be crucial for the production of prostaglandins in the fetal membranes prior to the onset of labor.

Prostaglandins that increase renin production in response to ACE inhibition are not derived from cyclooxygenase-1

2002 ◽  
Vol 283 (3) ◽  
pp. R638-R646 ◽  
Author(s):  
Hui-Fang Cheng ◽  
Sue-Wan Wang ◽  
Ming-Zhi Zhang ◽  
James A. McKanna ◽  
Richard Breyer ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Enzyme Inhibitor ◽  
Plasma Renin ◽  
Immunohistochemical Analysis ◽  
Renin Activity ◽  
Prostaglandin E ◽  
Receptor Subtype ◽  
Renin Mrna ◽  
Cox 2 ◽  
Cox 1

It is well known that nonselective, nonsteroidal anti-inflammatory drugs inhibit renal renin production. Our previous studies indicated that angiotensin-converting enzyme inhibitor (ACEI)-mediated renin increases were absent in rats treated with a cyclooxygenase (COX)-2-selective inhibitor and in COX-2 −/− mice. The current study examined further whether COX-1 is also involved in mediating ACEI-induced renin production. Because renin increases are mediated by cAMP, we also examined whether increased renin is mediated by the prostaglandin E2 receptor EP2 subtype, which is coupled to Gs and increases cAMP. Therefore, we investigated if genetic deletion of COX-1 or EP2 prevents increased ACEI-induced renin expression. Age- and gender-matched wild-type (+/+) and homozygous null mice (−/−) were administered captopril for 7 days, and plasma and renal renin levels and renal renin mRNA expression were measured. There were no significant differences in the basal level of renal renin activity from plasma or renal tissue in COX-1 +/+ and −/− mice. Captopril administration increased renin equally [plasma renin activity (PRA): +/+ 9.3 ± 2.2 vs. 50.1 ± 10.9; −/− 13.7 ± 1.5 vs. 43.9 ± 6.6 ng ANG I · ml−1 · h−1; renal renin concentration: +/+ 11.8 ± 1.7 vs. 35.3 ± 3.9; −/− 13.0 ± 3.0 vs. 27.8 ± 2.7 ng ANG I · mg protein−1 · h−1; n = 6; P < 0.05 with or without captopril]. ACEI also increased renin mRNA expression (+/+ 2.4 ± 0.2; −/− 2.1 ± 0.2 fold control; n = 6–10; P < 0.05). Captopril led to similar increases in EP2 −/− compared with +/+. The COX-2 inhibitor SC-58236 blocked ACEI-induced elevation in renal renin concentration in EP2 null mice (+/+ 24.7 ± 1.7 vs. 9.8 ± 0.4; −/− 21.1 ± 3.2 vs. 9.3 ± 0.4 ng ANG I · mg protein−1 · h−1; n = 5) as well as in COX-1 −/− mice (SC-58236-treated PRA: +/+ 7.3 ± 0.6; −/− 8.0 ± 0.9 ng ANG I · ml−1 · h−1; renal renin: +/+ 9.1 ± 0.9; −/− 9.6 ± 0.5 ng ANG I · mg protein−1 · h−1; n = 6–7; P < 0.05 compared with no treatment). Immunohistochemical analysis of renin expression confirmed the above results. This study provides definitive evidence that metabolites of COX-2 rather than COX-1 mediate ACEI-induced renin increases. The persistent response in EP2 nulls suggests involvement of prostaglandin E2 receptor subtype 4 and/or prostacyclin receptor (IP).

Abstract 322: Cyclooxygenase (COX) Inhibition Prior to CPR Decreases Heart Rate Variability in Pigs

Circulation ◽  
2018 ◽  
Vol 138 (Suppl_2) ◽  
Author(s):  
Jose A Adams ◽  
Arkady Uryash ◽  
Jose R Lopez
Keyword(s):  
Heart Rate ◽  
Heart Rate Variability ◽  
Troponin I ◽  
Prostaglandin Synthesis ◽  
Cyclooxygenase Inhibitors ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Cox 2 ◽  
The Impact ◽  
Cox 1

Background: Cyclooxygenase inhibitors (COX-1 and 2) are widely used and inhibit prostaglandin synthesis. COX inhibitors have been shown to increase overall cardiovascular risk. Heart rate variability (HRV) is a measure of the balance of autonomic nervous system and shown to be predictive of neurological outcome after cardiac arrest. Prostaglandins are cardioprotective and modulate HRV. We hypothesized that prostaglandin inhibition impacts short term CPR survival and outcomes based on HRV in swine. Methods: 24 animals (30±5kg) were randomized to pretreatment with indomethacin (I) 2mg/kg (COX-1 Inhibitor), Celecoxib (C) 2mg/kg (COX-2 inhibitor) or placebo (P). VF was induced and after 3 minutes all animals received chest compression and ventilation. After 18 minutes of VF, vasopressin given and defibrillation attempted. Electrocardiogram, echocardiogram and hemodynamic measurements done at baseline (BL), after infusions (Tx) and return of spontaneous circulation (ROSC) at 30 and 180 minutes. Results: ROSC was achieved; 3/8 (I) compared with 7/8 (C), and 7/8 (P). No differences in blood gases or hemodynamics pre, during or post CPR between groups. Echo showed decrease function post resuscitation in surviving animals but not significantly different among groups. COX-2 inhibition induced a significant decrease in linear (SDNN, RMSSD) and frequency (HF) measures of HRV towards greater sympathetic tone, post resuscitation. Compared to P, COX-2 inhibition increased Troponin I levels at 180 min after ROSC; P [84(4)] vs C [721(31)] mg/dl (p< 0.001). Conclusions: COX-1 inhibition decreases ROSC, whereas COX-2 inhibition significantly increases indices of myocardial tissue damage, and decreases HRV. The impact on long term outcome is unknown. Since many adults use COX-1 or COX-2 inhibitors, studies analyzing post resuscitation outcomes of patients should consider the effects of prostaglandin synthesis inhibitors as confounding variables.

scholarly journals Cyclooxygenase-1 and -2 Differentially Modulate Lipopolysaccharide-Induced Blood–Brain Barrier Disruption through Matrix Metalloproteinase Activity

2009 ◽  
Vol 30 (2) ◽  
pp. 370-380 ◽  
Author(s):  
Saba Aid ◽  
Afonso C Silva ◽  
Eduardo Candelario-Jalil ◽  
Sang-Ho Choi ◽  
Gary A Rosenberg ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Mrna Expression ◽  
Blood Brain Barrier ◽  
Immune Activation ◽  
Innate Immune ◽  
Brain Barrier ◽  
Innate Immune Activation ◽  
Blood Brain ◽  
Cox 2 ◽  
Cox 1

Cyclooxygenases (COX) -1 and -2 are key regulators of innate immune responses. We recently demonstrated that the expression of proinflammatory cytokines and chemokines is reduced in COX-1 null (−/−), and increased in COX-2−/− mice compared with their respective wild type controls during lipopolysaccharide (LPS)-induced innate immune activation. As chemokines are involved in leukocyte recruitment into the inflamed brain, we hypothesized that COX-1 and COX-2 deletion will differentially modulate blood–brain barrier (BBB) permeability in response to LPS. In the present study, using quantitative magnetic resonance imaging, we found that LPS-induced BBB disruption was exacerbated in COX-2−/− versus COX-2+/+ mice. In the hippocampus and cortex of LPS-treated mice, matrix metalloproteinase (MMP)-3 activity was significantly decreased in COX-1−/− mice, whereas in COX-2−/− mice the activity of both MMP-9 and MMP-3, known to mediate BBB breakdown, was increased. Brain mRNA expression of the leukocyte attracting chemokine Cxcl10, the intercellular interaction molecule Icam-1, the pan-leukocyte marker Cd45 was increased in COX-2−/− versus COX-2+/+ mice, whereas Cxcl10 and Cd45 mRNA expression was decreased in COX-1−/− versus COX-1+/+ mice after LPS. Altogether, these results indicate that COX-2 activity modulates MMP-9 and-3 activities and is necessary to maintain BBB integrity during toll-like receptor 4-dependent innate immune activation.

Differential Regulation of Cyclo-Oxygenase-1 and Cyclo-Oxygenase-2 Gene Expression by Lipopolysaccharide Treatment in vivo in the Rat

1996 ◽  
Vol 90 (4) ◽  
pp. 301-306 ◽  
Author(s):  
Shu Fang Liu ◽  
Robert Newton ◽  
Timothy W. Evans ◽  
Peter J. Barnes
Keyword(s):  
Mrna Expression ◽  
Down Regulation ◽  
Physiological Conditions ◽  
Prostaglandin Release ◽  
Key Enzyme ◽  
Cox 2 ◽  
Oxide Synthase ◽  
Cox 1 ◽  
Inducible Nitric Oxide

1. Prostaglandins are important regulatory mediators of cardiovascular and pulmonary functions which may become disordered in patients with sepsis. The mechanisms controlling their synthesis and release under these circumstances remain unclear. Cyclo-oxygenase (COX, prostaglandin G/H synthase) is a key enzyme in prostaglandin synthesis and has two isoforms (COX-1 and COX-2). COX-1 is constitutively expressed and is probably responsible for prostaglandin release under physiological conditions, whereas COX-2 is expressed at high levels upon induction. 2. We investigated the effect of lipopolysaccharide treatment in vivo on differential COX-1 and COX-2 mRNA expression in the rat. 3. The 2.8 kb COX-1 message was detected in all lungs and seven hearts of eight control rats. In lipopolysaccharide-treated animals, COX-1 expression was reduced by approximately 5-fold in lungs and 2-fold in hearts as quantified by densitometry. In parallel, a marked upregulation of COX-2 mRNA expression was observed. The 4.4 kb COX-2 transcript was absent or expressed at low level in control lungs and hearts, but was increased by approximately 7- and 12-fold in lipopolysaccharide-treated lungs and hearts respectively. Neither the down-regulation of COX-1 nor the upregulation of COX-2 mRNA induced by lipopolysaccharide was significantly affected by pretreatment with dexamethasone in lung and heart, although expression of inducible nitric oxide synthase, induced by lipopolysaccharide, was markedly inhibited in the same tissues. 4. The down-regulation of COX-1 and upregulation of COX-2 may contribute to the multi-organ failure seen in sepsis.

Genetic Evidence for Distinct Roles of COX-1 and COX-2 in the Immediate and Delayed Phases of Prostaglandin Synthesis in Mast Cells

1999 ◽  
Vol 265 (1) ◽  
pp. 205-210 ◽  
Author(s):  
Srinivasa T. Reddy ◽  
Howard F. Tiano ◽  
Robert Langenbach ◽  
Scott G. Morham ◽  
Harvey R. Herschman
Keyword(s):  
Mast Cells ◽  
Prostaglandin Synthesis ◽  
Genetic Evidence ◽  
Cox 2 ◽  
Cox 1

scholarly journals The potential of acetylsalicylic acid and vitamin E in modulating inflammatory cascades in chickens under lipopolysaccharide-induced inflammation

2019 ◽  
Vol 50 (1) ◽  
Author(s):  
Paweł Konieczka ◽  
Marcin Barszcz ◽  
Paweł Kowalczyk ◽  
Michał Szlis ◽  
Jan Jankowski
Keyword(s):  
Gene Expression ◽  
Oxygen Consumption ◽  
Vitamin E ◽  
Acetylsalicylic Acid ◽  
Mrna Expression ◽  
Poultry Production ◽  
Lps Challenge ◽  
Immune Tissues ◽  
Cox 2 ◽  
Cox 1

Abstract Distinct enzymes, including cyclooxygenase 1 and 2 (COX-1 and COX-2), lipoxygenase (LOXs), and cytochrome P450 monooxygenase (CYP450), produce different stress mediators and mediate inflammation in birds. Bioactive agents such as acetylsalicylic acid (ASA) and vitamin E (vE) may affect enzyme activities and could be used in poultry production to control the magnitude of acute phase inflammation. Here, we characterized COX, LOX, and CYP450 mRNA expression levels in chicken immune tissues in response to Escherichia coli lipopolysaccharide (LPS) challenge and investigated whether ASA and vE could alter gene expression. Additionally, for the first time in chickens, we evaluated oxygen consumption by platelet mitochondria as a biomarker of mitochondria function in response to ASA- and vE. LPS challenge compromised bird growth rates, but neither dietary ASA nor vE significantly ameliorated this effect; however, gradually increasing dietary vE levels were more effective than basal levels. ASA regulated arachidonic acid metabolism, providing an eicosanoid synthesis substrate, whereas gradually increasing vE levels evoked aspirin resistance during challenge. Gene expression in immune tissues was highly variable, indicating a complex regulatory network controlling inflammatory pathways. However, unlike COX-1, COX-2 and CYP450 exhibited increased mRNA expression in some cases, suggesting an initiation of novel anti-inflammatory and pro-resolving signals during challenge. Measuring oxygen consumption rate, we revealed that neither the ASA nor vE levels applied here exerted toxic effects on platelet mitochondria.

Sign in / Sign up

Export Citation Format

Share Document