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 Cross-linking of the high-affinity IgE receptor induces the expression of cyclo-oxygenase 2 and attendant prostaglandin generation requiring interleukin 10 and interleukin 1β in mouse cultured mast cells

1996 ◽  
Vol 320 (3) ◽  
pp. 965-973 ◽  
Author(s):  
Musharraf ASHRAF ◽  
Makoto MURAKAMI ◽  
Ichiro KUDO
Keyword(s):  
Mast Cells ◽  
Mrna Level ◽  
Interleukin 10 ◽  
Second Phase ◽  
Mouse Bone Marrow ◽  
Cox 2 ◽  
The Individual ◽  
High Affinity Ige Receptor ◽  
Delayed Phase ◽  
Cox 1

When mouse bone marrow-derived mast cells (BMMC) developed in interleukin (IL)-3 were activated with IgE and antigen (IgE/antigen) in the presence of both IL-10 and IL-1β, two sequential phases of prostaglandin (PG)D2 generation were elicited, in which the first phase occurred by 1 h and the second phase from 2 to 10 h. The delayed phase of PGD2 generation was accompanied by a marked induction of cyclo-oxygenase (COX)-2 mRNA, which reached a peak at 1–2 h, followed by that of its protein from 2–10 h, with a peak at 5 h. The immediate phase of PGD2 generation was completely abrogated by the irreversible inhibition of pre-exisiting COX-1 by aspirin pretreatment, whereas the delayed phase of PGD2 generation was almost undetectable in the presence of the COX-2 inhibitor NS-398. A detailed analysis of the individual effects of IgE/antigen, IL-10 and IL-1β on COX-2 expression revealed that IgE/antigen and IL-10 each initiated and stabilized COX-2 mRNA expression, leading to an increase in the expression of its protein. Conversely, IL-1β stabilized the COX-2 protein without affecting its mRNA level. The induction of COX-2 by IgE/antigen with IL-10 and IL-1β preceded the induction of transcripts for endogenous cytokines such as IL-6, IL-1β and IL-10. The inhibition of PGD2 generation by indomethacin did not affect the induction of COX-2 or these cytokines. Thus the two major delayed-phase responses of BMMC after IgE-dependent activation, namely COX-2-dependent PGD2 generation and cytokine production, are regulated independently.

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.

scholarly journals Differential usage of COX-1 and COX-2 in prostaglandin production by mast cells and basophils

2017 ◽  
Vol 10 ◽  
pp. 82-87 ◽  
Author(s):  
Tomoyuki Bando ◽  
Setsuko Fujita ◽  
Naoko Nagano ◽  
Soichiro Yoshikawa ◽  
Yoshinori Yamanishi ◽  
...  
Keyword(s):  
Mast Cells ◽  
Prostaglandin Production ◽  
Cox 2 ◽  
Cox 1

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 Resident peritoneal macrophages and mast cells are important cellular sites of COX-1 and COX-2 activity during acute peritoneal inflammation

2009 ◽  
Vol 57 (6) ◽  
pp. 459-466 ◽  
Author(s):  
Elzbieta Kolaczkowska ◽  
Anna Goldys ◽  
Elzbieta Kozakiewicz ◽  
Monika Lelito ◽  
Barbara Plytycz ◽  
...  
Keyword(s):  
Mast Cells ◽  
Peritoneal Macrophages ◽  
Peritoneal Inflammation ◽  
Cox 2 ◽  
Cox 1

Histamine-dependent prolongation by aldosterone of vasoconstriction in isolated small mesenteric arteries of the mouse

2013 ◽  
Vol 304 (8) ◽  
pp. H1094-H1102 ◽  
Author(s):  
Jeppe Schjerning ◽  
Torben R. Uhrenholt ◽  
Per Svenningsen ◽  
Paul M. Vanhoutte ◽  
Ole Skøtt ◽  
...  
Keyword(s):  
Mast Cells ◽  
Receptor Antagonist ◽  
Vascular Function ◽  
Mesenteric Arteries ◽  
Wild Type ◽  
Rt Pcr ◽  
No Donor ◽  
High K ◽  
Cox 2 ◽  
Cox 1

In arterioles, aldosterone counteracts the rapid dilatation (recovery) following depolarization-induced contraction. The hypothesis was tested that this effect of aldosterone depends on cyclooxygenase (COX)-derived products and/or nitric oxide (NO) synthase (NOS) inhibition. Recovery of the response to high K+ was observed in mesenteric arteries of wild-type and COX-2−/− mice but it was significantly diminished in preparations from endothelial NOS (eNOS)−/− mice. Aldosterone pretreatment inhibited recovery from wild-type and COX-2−/− mice. The NO donor sodium nitroprusside (SNP) restored recovery in arteries from eNOS−/− mice, and this was inhibited by aldosterone. Actinomycin-D abolished the effect of aldosterone, indicating a genomic effect. The effect was blocked by indomethacin and by the COX-1 inhibitor valeryl salicylate but not by NS-398 (10−6 mol/l) or the TP-receptor antagonist S18886 (10−7 mol/l). The effect of aldosterone on recovery in arteries from wild-type mice and the SNP-mediated dilatation in arteries from eNOS−/− mice was inhibited by the histamine H2 receptor antagonist cimetidine. RT-PCR showed expression of mast cell markers in mouse mesenteric arteries. The adventitia displayed granular cells positive for toluidine blue vital stain. Confocal microscopy of live mast cells showed loss of quinacrine fluorescence and swelling after aldosterone treatment, indicating degranulation. RT-PCR showed expression of mineralocorticoid receptors in mesenteric arteries and in isolated mast cells. These findings suggest that aldosterone inhibits recovery by stimulation of histamine release from mast cells along mesenteric arteries. The resulting activation of H2 receptors decreases the sensitivity to NO of vascular smooth muscle cells. Aldosterone may chronically affect vascular function through paracrine release of histamine.

Expression and role of cyclooxygenase isoforms in alveolar and peritoneal macrophages

1995 ◽  
Vol 268 (2) ◽  
pp. L294-L301 ◽  
Author(s):  
J. Wilborn ◽  
D. L. DeWitt ◽  
M. Peters-Golden
Keyword(s):  
Steady State ◽  
Cell Types ◽  
Peritoneal Macrophages ◽  
Prostaglandin Synthesis ◽  
Steady State Levels ◽  
Cox 2 ◽  
Synthetic Capacity ◽  
Cyclooxygenase Isoforms ◽  
Cox 1

Prostaglandin synthesis represents one means by which macrophages modulate inflammation. The initial enzyme in the metabolism of arachidonic acid to prostaglandins is cyclooxygenase (COX). Both constitutive (COX-1) and inducible (COX-2) isoforms are recognized. We previously showed that COX activity of rat peritoneal macrophages (PM) exceeds that of alveolar macrophages (AM). In this study, we correlated the steady-state levels of COX-1 and COX-2 proteins with COX activity in resident AM and PM. Freshly obtained AM contained lower levels of COX-1 than did fresh PM. Neither contained substantial amounts of COX-2 in the basal state, but both cell types demonstrated induction when cultured with lipopolysaccharide; once again, COX-2 levels in PM exceeded those in AM. Despite COX-2 induction under these circumstances, its contribution to prostaglandin production appeared to be modest. We conclude that, although both isoforms of COX are expressed in rat AM and PM, COX-1 is responsible for the majority of enzyme activity in both the basal and stimulated states. The lesser prostaglandin synthetic capacity of AM than of PM appears to be the consequence of lower steady-state levels of both COX proteins.

scholarly journals Suppressive role of PPARγ in the IgE-dependent activation of mast cells

2019 ◽  
Author(s):  
Kazuki Nagata ◽  
Kazumi Kasakura ◽  
Ryosuke Miura ◽  
Takuya Yashiro ◽  
Chiharu Nishiyama
Keyword(s):  
Mast Cells ◽  
Expression Level ◽  
Cell Surface Expression ◽  
Mrna Levels ◽  
Cox Inhibitor ◽  
Pparγ Agonist ◽  
Ige Mediated ◽  
Cox 2 ◽  
Cox 1

Abstract Mast cells (MCs) play a central role in IgE-dependent immune responses. PPARγ is a nuclear receptor that is essential for adipocyte differentiation and insulin sensitivity. Although PPARγ is expressed in activated MCs, the effect of PPARγ suppression in IgE-mediated activation of MCs is largely unknown. In the current study, we evaluated the effect of PPARγ knockdown on the function of IgE plus antigen (Ag)-stimulated MCs using siRNA-transfected BMMCs. We found that the mRNA expression level of cytokines in IgE/Ag-stimulated BMMCs was significantly increased in PPARγ knockdown BMMCs, and IgE/Ag-mediated degranulation and the protein production level of TNF-α was moderately increased by PPARγ knockdown, whereas the cell surface expression level of FcεRI was not affected by PPARγ knockdown. Oral administration of pioglitazone (PPARγ agonist) significantly suppressed body temperature change of mice in passive systemic anaphylaxis, supporting the inhibitory functions of PPARγ in IgE/Ag-dependent activation of MCs in vivo. IgE-mediated upregulation of mRNA levels of Ptgs2 (encoding COX-2) was drastically enhanced in PPARγ knockdown BMMCs. Although several prostaglandin (PG) derivatives are known to be ligands for PPARγ, treatment with a COX inhibitor, acetyl salicylic acid, upregulated the IgE-mediated increase of Il13, Tnf, and Ptgs2 mRNA levels in a synergistic manner with PPARγ siRNA. Knockdown of COX-1 and/or COX-2 by siRNA showed that suppression of IgE/Ag-mediated activation was mainly dependent on COX-1. Taken together, these results indicate that PPARγ suppresses IgE/Ag-induced transactivation of cytokine genes and the Ptgs2 gene in MCs in a manner distinguishable from that of PGs.

COX and PTGDS Gene Expression Levels in PGD2 Synthesis Pathway are Correlated with miR-520 in Patients with Vessel Restenosis

2020 ◽  
Vol 20 (9) ◽  
pp. 1514-1522 ◽  
Author(s):  
Shima Rezaee ◽  
Naser Kakavandi ◽  
Mohammad Shabani ◽  
Mohsen Khosravi ◽  
Seyed R. Hosseini-Fard ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prostaglandin Synthesis ◽  
Expression Levels ◽  
Stent Restenosis ◽  
Subendothelial Space ◽  
Elisa Technique ◽  
Cox 2 ◽  
Cox 1 ◽  
In Stent Restenosis ◽  
Gene Expression Levels

Background: The vessel restenosis is related to the inflammatory events in subendothelial space. It is proposed that the inflammatory agents affect the prostaglandin synthesis pathway. In this study, we investigated the COX-1, COX-2, PTGDS and miRNA-520a-5p expression levels and the serum 15-Deoxy-Δ12,14-PGJ2 metabolite values in patients with the stenosed and re-stenosed vessels. Furthermore, the associations between genes and miR-520 were evaluated in the monocyte transfection studies. Methods: The subjects (n=60) were included three groups; healthy subjects (control (stenosis < 5%), stent no restenosis (SNR, restenosis < 5%) and in-stent restenosis (ISR, restenosis > 70%)). The miRNA and gene expression levels were measured by RT-qPCR technique. 15-Deoxy-Δ12,14-PGJ2 values were measured by the ELISA technique. The miR-520 was transfected into myocytes using PEI polymer. Results: The monocyte COX-1, COX-2 and PTGDS gene expression levels and the serum 15-Deoxy- Δ12,14-PGJ2 values increased significantly in the patients. Furthermore, the miR-520 correlated conversely with the COX-1, and PTGDS gene expression levels. Conclusion: The results showed that the PGD2 synthesis pathway is active in the patients and, miR- 520 may be involved in the function of this pathway.

scholarly journals Zymosan-induced glycerylprostaglandin and prostaglandin synthesis in resident peritoneal macrophages: roles of cyclo-oxygenase-1 and -2

2006 ◽  
Vol 399 (1) ◽  
pp. 91-99 ◽  
Author(s):  
Carol A. Rouzer ◽  
Susanne Tranguch ◽  
Haibin Wang ◽  
Hao Zhang ◽  
Sudhansu K. Dey ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Peritoneal Macrophages ◽  
Prostaglandin Synthesis ◽  
Wild Type ◽  
Cytosolic Phospholipase ◽  
Cytosolic Phospholipase A2α ◽  
Cox 2 ◽  
Cox 1 ◽  
Exogenous Substrates

COX [cyclo-oxygenase; PG (prostaglandin) G/H synthase] oxygenates AA (arachidonic acid) and 2-AG (2-arachidonylglycerol) to endoperoxides that are converted into PGs and PG-Gs (glycerylprostaglandins) respectively. In vitro, 2-AG is a selective substrate for COX-2, but in zymosan-stimulated peritoneal macrophages, PG-G synthesis is not sensitive to selective COX-2 inhibition. This suggests that COX-1 oxygenates 2-AG, so studies were carried out to identify enzymes involved in zymosan-dependent PG-G and PG synthesis. When macrophages from COX-1−/− or COX-2−/− mice were treated with zymosan, 20–25% and 10–15% of the PG and PG-G synthesis observed in wild-type cells respectively was COX-2 dependent. When exogenous AA and 2-AG were supplied to COX-2−/− macrophages, PG and PG-G synthesis was reduced as compared with wild-type cells. In contrast, when exogenous substrates were provided to COX-1−/− macrophages, PG-G but not PG synthesis was reduced. Product synthesis also was evaluated in macrophages from cPLA2α (cytosolic phospholipase A2α)−/− mice, in which zymosan-induced PG synthesis was markedly reduced, and PG-G synthesis was increased approx. 2-fold. These studies confirm that peritoneal macrophages synthesize PG-Gs in response to zymosan, but that this process is primarily COX-1-dependent, as is the synthesis of PGs. They also indicate that the 2-AG and AA used for PG-G and PG synthesis respectively are derived from independent pathways.

Sign in / Sign up

Export Citation Format

Share Document