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 The immediate phase of c-kit ligand stimulation of mouse bone marrow-derived mast cells elicits rapid leukotriene C4 generation through posttranslational activation of cytosolic phospholipase A2 and 5-lipoxygenase.

1995 ◽  
Vol 182 (1) ◽  
pp. 197-206 ◽  
Author(s):  
M Murakami ◽  
K F Austen ◽  
J P Arm
Keyword(s):  
Bone Marrow ◽  
Arachidonic Acid ◽  
Mast Cells ◽  
Cell Membrane ◽  
Phospholipase A2 ◽  
Mouse Bone Marrow ◽  
Kit Ligand ◽  
Cytosolic Phospholipase ◽  
Delayed Phase ◽  
Stimulation Of

c-kit ligand (KL) activated mouse bone marrow-derived mast cells (BMMC) for the dose- and time-dependent release of arachidonic acid from cell membrane phospholipids, with generation of leukotriene (LT) C4 in preference to prostaglandin (PG)D2. KL at concentrations of 10 ng/ml elicited half-maximal eicosanoid generation and at concentrations of > 50 ng/ml elicited a maximal generation of approximately 15 ng LTC4 and 1 ng PGD2 per 10(6) cells, with 20% net beta-hexosaminidase release 10 min after stimulation. Of the other cytokines tested, none, either alone or in combination with KL, elicited or modulated the immediate phase of mediator release by BMMC, indicating strict specificity for KL. Activation of BMMC in response to KL was accompanied by transient phosphorylation of cytosolic phospholipase A2 and reversible translocation of 5-lipoxygenase to a cell membrane fraction 2-5 min after stimulation, when the rate of arachidonic acid release and LTC4 production were maximal. BMMC continuously exposed to KL in the presence of IL-10 and IL-1 beta generated LTC4 in marked preference to PGD2 over the first 10 min followed by delayed generation of PGD2 with no LTC4 over several hours. Pharmacologic studies revealed that PGD2 generation in the immediate phase depended on prostaglandin endoperoxide synthase (PGHS)-1 and in the delayed phase on PGHS-2. Thus, KL provided a nonallergic stimulus for biphasic eicosanoid generation by mast cells. The immediate phase is dominated by LTC4 generation with kinetics and postreceptor biosynthetic events similar to those observed after cell activation through the high affinity IgE receptor, whereas the delayed phase of slow and selective PGD2 production is mediated by induction of PGHS-2.

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

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

scholarly journals Cyclo-oxygenase-2 contributes to constitutive prostanoid production in rat kidney and brain

2005 ◽  
Vol 391 (3) ◽  
pp. 561-566 ◽  
Author(s):  
Pierre-Olivier Hétu ◽  
Denis Riendeau
Keyword(s):  
Rat Kidney ◽  
Significant Inhibition ◽  
Complete Analysis ◽  
Inflammatory Conditions ◽  
Prostanoid Production ◽  
Cox 2 ◽  
The Individual ◽  
Cox 2 Inhibitors ◽  
Cox 1 ◽  
Prostanoid Synthesis

Cyclo-oxygenases (COXs) catalyse the synthesis of PGH2 (prostaglandin H2), which serves as the common substrate for the production of PGE2, PGD2, PGF2α, prostacyclin (or PGI2) and TXs (thromboxanes). While COX-1 is the major isoform responsible for prostanoid synthesis in healthy tissues, little information is available on the contribution of constitutive COX-2 to the various prostanoid synthetic pathways under non-inflammatory conditions. To evaluate further the role of COX-2 in prostanoid biosynthesis, rats were acutely treated with the selective COX-1 inhibitor SC-560 [5-(4-chlorophenyl)-1-(4-methoxyphenyl)-3-trifluoromethylpyrazole] or the selective COX-2 inhibitors MF tricyclic [3-(3,4-difluorophenyl)-4-(4-(methylsulphonyl)phenyl)-2-(5H)-furanone] and DFU [5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulphonyl)phenyl-2-(5H)-furanone]. Selected tissues were then processed for a complete analysis of their prostanoid content by liquid chromatography MS. Whereas the treatment with SC-560 caused a 60–70% inhibition in the total prostanoid content of most tissues examined, a significant decrease (35–50%) in total prostanoid content following selective COX-2 inhibition was solely detected for kidney and brain tissues. Analysis of the individual prostanoids reveals significant inhibition of 6-oxo-PGF1α, PGE2, PGD2, PGF2α and TXB2 in the kidney and inhibition of all these prostanoids with the exception of PGD2 in the forebrain. These results demonstrate that constitutively expressed COX-2 contributes to the production of prostanoids in kidney and brain for each of the PGE2, PGI2 and TXB2 pathways under non-inflammatory conditions. Approaches to modulate inflammation through specific inhibition of terminal synthases, such as mPGES-1 (microsomal PGE2 synthase-1), thus have the potential to differ from COX-2 inhibitors and non-selective non-steroidal anti-inflammatory drugs with regard to effects on constitutive prostanoid synthesis and on renal function.

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

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.

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.

scholarly journals Up-regulation of cytosolic prostaglandin E synthase in fetal-membrane and amniotic prostaglandin E2 accumulation in labor

PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0250638
Author(s):  
Nanase Takahashi ◽  
Toshiaki Okuno ◽  
Hiroki Fujii ◽  
Shintaro Makino ◽  
Masaya Takahashi ◽  
...  
Keyword(s):  
Amniotic Fluid ◽  
Mrna Level ◽  
Fetal Membrane ◽  
Prostaglandin E ◽  
Mrna Levels ◽  
Prostaglandin E Synthase ◽  
Detailed Mechanism ◽  
Human Labor ◽  
Cox 2 ◽  
Cox 1

Prostaglandin E2 (PGE2) is known to have important roles in labor, but the detailed mechanism underlying the spontaneous human labor remains unknown. Here, we examined the involvement of prostaglandin biosynthetic enzymes and transporter in the accumulation of PGE2 in amniotic fluid in human labor. PGE2 and its metabolites were abundant in amniotic fluid in deliveries at term in labor (TLB), but not at term not in labor (TNL). In fetal-membrane Transwell assays, levels of PGE2 production in both maternal and fetal compartments were significantly higher in the TLB group than the TNL group. In fetal-membrane, the mRNA level of PTGES3, which encodes cytosolic prostaglandin E synthase (cPGES), was significantly higher in TLB than in TNL, but the mRNA levels of the other PGE2-synthase genes were not affected by labor. Moreover, the mRNA level of PTGS2, which encodes cyclooxygenase-2 (COX-2) in the amnion was significantly higher in TLB than in TNL. Western blot analyses revealed that the levels of COX-1 and COX-2 were comparable between the two groups, however, the level of cPGES was relatively higher in TLB than in TNL. COXs, cPGES, and prostaglandin transporter (SLCO2A1) proteins were all expressed in both chorionic trophoblasts and amniotic epithelium. These findings suggest that COXs, cPGES and SLCO2A1 contribute to PGE2 production from fetal-membrane in labor.

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