scholarly journals Fluid Secretion Caused by Aerolysin-Like Hemolysin of Aeromonas sobria in the Intestines Is Due to Stimulation of Production of Prostaglandin E2 via Cyclooxygenase 2 by Intestinal Cells

2007 ◽  
Vol 76 (3) ◽  
pp. 1076-1082 ◽  
Author(s):  
Yoshio Fujii ◽  
Ken Tsurumi ◽  
Masaaki Sato ◽  
Eizo Takahashi ◽  
Keinosuke Okamoto
Keyword(s):  
Intestinal Mucosa ◽  
Fluid Secretion ◽  
Cyclooxygenase 2 ◽  
Prostaglandin E ◽  
Camp Production ◽  
Fluid Accumulation ◽  
Protein Levels ◽  
Aeromonas Sobria ◽  
Cox 2 ◽  
Cox 1

ABSTRACT To clarify the mechanisms of diarrheal disease induced by Aeromonas sobria, we examined whether prostaglandin E2 (PGE2) was involved in the intestinal secretory action of A. sobria hemolysin by use of a mouse intestinal loop model. The amount of PGE2 in jejunal fluid and the fluid accumulation ratio were directly related to the dose of hemolysin. The increase over time in the level of PGE2 was similar to that of the accumulated fluid. In addition, hemolysin-induced fluid secretion and PGE2 synthesis were inhibited by the selective cyclooxygenase 2 (COX-2) inhibitor NS-398 but not the COX-1 inhibitor SC-560. Western blot analysis revealed that hemolysin increased the COX-2 protein levels but reduced the COX-1 protein levels in mouse intestinal mucosa in vivo. These results suggest that PGE2 functions as an important mediator of diarrhea caused by hemolysin and that PGE2 is produced primarily through a COX-2-dependent mechanism. Subsequently, we examined the relationship between PGE2, cyclic AMP (cAMP), and cystic fibrosis transmembrane conductance regulator (CFTR) Cl− channels in mouse intestinal mucosa exposed to hemolysin. Hemolysin increased the levels of cAMP in the intestinal mucosa. NS-398 inhibited the increase in cAMP production, but SC-560 did not. In addition, H-89, a cAMP-dependent protein kinase A (PKA) inhibitor, and glibenclamide, a CFTR inhibitor, inhibited fluid accumulation. Taken together, these results indicate that hemolysin activates PGE2 production via COX-2 and that PGE2 stimulates cAMP production. cAMP then activates PKA, which in turn stimulates CFTR Cl− channels and finally leads to fluid accumulation in the intestines.

Effect of COX-2 inhibitor NS-398 on expression of PGE2 receptor subtypes in M-1 mouse CCD cells

2001 ◽  
Vol 281 (1) ◽  
pp. F123-F132 ◽  
Author(s):  
Rania Nasrallah ◽  
Odette Laneuville ◽  
Shawn Ferguson ◽  
Richard L. Hébert
Keyword(s):  
Collecting Duct ◽  
Specific Inhibitor ◽  
Receptor Expression ◽  
Receptor Protein ◽  
Prostaglandin E ◽  
Receptor Subtype ◽  
Receptor Subtypes ◽  
Camp Production ◽  
Protein Levels ◽  
Cox 2

Our present study has investigated the effect of cyclooxygenase-2 (COX-2) inhibition on prostaglandin E2 (PGE2) receptor expression in M-1 cortical collecting duct cells and measured their response to PGE2. Using a semiquantitative titration analysis method, we show that following the addition of the COX-2-specific inhibitor NS-398, E-prostanoid receptor subtype (EP3 and EP4) mRNA expression was found to increase threefold each vs. the vehicle-treated control. We also observed that EP1but not EP2 is expressed in M-1 cells and EP2levels are not induced by NS-398. To determine the status of the PGE2 response on exposure to NS-398, we measured cAMP levels in cells after stimulation with varying concentrations of PGE2, then pretreated the cells with 10 μM NS-398 before PGE2 exposure and found a significant rise in the stimulatory effect of PGE2 on cAMP production. Finally, Western blot analysis of the levels of the EP4 receptor protein in control vs. NS-398-treated cells revealed an induction in protein levels in these cells, correlating with the induction in EP4 mRNA. We conclude that NS-398 upregulates the expression of EP3 and EP4 mRNA in M-1 cells. Also, EP4 protein levels are increased, resulting in an increased stimulation of cAMP production by PGE2.

scholarly journals Role of Cyclooxygenase Enzymes in a Murine Model of Experimental Cholera

2003 ◽  
Vol 71 (11) ◽  
pp. 6234-6242 ◽  
Author(s):  
Deborah L. Gessell-Lee ◽  
Vsevolod L. Popov ◽  
Istvan Boldogh ◽  
Juan P. Olano ◽  
Johnny W. Peterson
Keyword(s):  
Oxidative Stress ◽  
Tissue Injury ◽  
Fluid Secretion ◽  
Fluid Accumulation ◽  
Acid Metabolites ◽  
Cox 2 ◽  
Small Intestinal ◽  
Cox 1 ◽  
Experimental Cholera

ABSTRACT Nonsteroidal anti-inflammatory drugs (e.g., indomethacin) inhibit and reduce the fluid secretion responses elicited by cholera toxin (CT), but it has not been conclusively determined which cyclooxygenase (COX) isoform is involved in CT's action. This study evaluated the role of the COX enzymes and their arachidonic acid metabolites in experimental cholera. Swiss-Webster mice were dosed with celecoxib and rofecoxib and challenged with CT in ligated small intestinal loops, and intestinal segments from mice deficient in COX-1 and COX-2 were challenged with CT. The effects of CT on fluid accumulation, prostaglandin E2 production, mucosal tissue injury, and markers of oxidative stress were measured. Celecoxib and rofecoxib given at 160 μg per mouse inhibited CT-induced fluid accumulation by 48% and 31%, respectively, but there was no significant difference among cox-1−/− and cox-2−/− mice in response to CT compared to wild-type controls. CT elevated tissue levels of oxidized glutathione and lipid peroxides and elicited small intestinal tissue injury in two of five cox-1−/− and four of five cox-2−/− mice. A role for COX-2 in CT's mechanism of action has previously been suggested by the effectiveness of COX-2 inhibitors in reducing CT-induced fluid secretion, but CT challenge of COX-1 and COX-2 knockout mice did not corroborate the pharmacological data. The results of this study show that CT induced oxidative stress in COX-deficient mice and suggest a tissue-protective role for arachidonic acid metabolites in the small intestine against oxidative stress.

scholarly journals Cyclooxygenase-1 and -2 Are Required for Production of Infectious Pseudorabies Virus

2004 ◽  
Vol 78 (23) ◽  
pp. 12964-12974 ◽  
Author(s):  
Neelanjana Ray ◽  
Margaret E. Bisher ◽  
L. W. Enquist
Keyword(s):  
Dna Cleavage ◽  
Pseudorabies Virus ◽  
Prostaglandin E ◽  
Viral Dna ◽  
Cox Inhibitors ◽  
Protein Levels ◽  
Early Protein ◽  
Empty Capsid ◽  
Cox 2 ◽  
Cox 1

ABSTRACT We have recently shown that cyclooxygenase-2 (COX-2) transcription is markedly induced after herpes simplex virus type 1 and pseudorabies virus (PRV) infections of rat embryonic fibroblast (REF) cells (N. Ray and L. W. Enquist, J. Virol. 78:3489-3501, 2004). For this study, we investigated the role of cyclooxygenase induction in the replication and growth of PRV. We demonstrate here a concordant increase in COX-2 mRNA and protein levels after the infection of REF cells. Inhibitors blocking the activity of cyclooxygenases caused a dramatic reduction in PRV growth. Viral growth could be restored if prostaglandin E2, the final product of COX-2 activity, was added simultaneously with the COX inhibitors. Immediate-early protein IE180, major capsid protein VP5, and glycoprotein expression were slightly reduced in the presence of COX-2 inhibitors, but expression of the early protein EP0 was not affected by COX inhibition. Viral DNA replication was marginally reduced in the presence of a COX-1/2 inhibitor, but there was no defect in viral DNA cleavage. Electron microscopy analysis revealed an increased number of unusual empty capsid structures in the nuclei of cells infected with PRV in the presence of a COX-1/2 inhibitor. These capsid structures shared some characteristics with procapsids but had a novel appearance by negative staining. Our data establish a role for COX-1 and COX-2 in facilitating the efficient growth and replication of PRV in primary cells.

Expressions of cyclooxygenase-2 (COX-2) and prostaglandin E receptors (EPs) in gallbladder carcinoma (GBca)-association with tumor progression

2001 ◽  
Vol 120 (5) ◽  
pp. A573-A573
Author(s):  
J SHODA ◽  
T ASANO ◽  
T KAWAMOTO ◽  
Y MATSUZAKI ◽  
N TANAKA ◽  
...  
Keyword(s):  
Tumor Progression ◽  
Gallbladder Carcinoma ◽  
Cyclooxygenase 2 ◽  
Prostaglandin E ◽  
Cox 2

scholarly journals Upregulation of Cyclooxygenase-2 (COX-2) and Microsomal Prostaglandin E 2 Synthase-1 (mPGES-1) in Wall of Ruptured Human Cerebral Aneurysms

Stroke ◽  
2012 ◽  
Vol 43 (7) ◽  
pp. 1964-1967 ◽  
Author(s):  
David Hasan ◽  
Tomoki Hashimoto ◽  
David Kung ◽  
R. Loch Macdonald ◽  
H. Richard Winn ◽  
...  
Keyword(s):  
Cerebral Aneurysms ◽  
Cyclooxygenase 2 ◽  
Prostaglandin E ◽  
Cox 2

Involvement of cyclooxygenase 2 (COX-2) in intrinsic tone of isolated guinea pig

1995 ◽  
Vol 73 (11) ◽  
pp. 1561-1567 ◽  
Author(s):  
L. Charette ◽  
C. Misquitta ◽  
J. Guay ◽  
D. Riendeau ◽  
T. R. Jones
Keyword(s):  
Guinea Pig ◽  
Time Course ◽  
Cyclooxygenase 2 ◽  
Maximal Response ◽  
Pharmacological Agents ◽  
Cyclooxygenase 1 ◽  
Inflammatory Drugs ◽  
Cox 2 ◽  
Cox 2 Inhibitors ◽  
Cox 1

Indomethacin and related nonsteroidal anti-inflammatory drugs relax prostanoid-dependent intrinsic tone of isolated guinea pig trachea by inhibiting cyclooxygenase (COX). Recently, a second isoform of COX (COX-2) was discovered, which differed from COX-1 with respect to protein structure, transcriptional regulation, and susceptibility to inhibition by pharmacological agents. It is now known that indomethacin nonselectively inhibits COX-1 and COX-2, whereas NS-398 is a selective inhibitor of COX-2. In the present study we compared the activity of a selective (NS-398) and nonselective (indomethacin) COX-2 inhibitor on intrinsic tone of isolated guinea pig trachea. NS-398 ≥ indomethacin produced a reversal of intrinsic tone with a similar concentration-dependent (10 nM to 1 μM) time course (Tmax approximately 20–45 min), potency (EC50 1.7 and 5.6 nM, respectively), and maximal response. Contractions to cholinergic nerve stimulation (45 V, 0.5 ms, 0.1–32 Hz) and histamine were similarly modulated in tissues relaxed with the selective or nonselective COX-2 inhibitors. Immunoblot analyses showed that COX-2 protein synthesis was induced in both the cartilage and smooth muscle portions of the trachea during changes in intrinsic tone. These findings are consistent with pharmacological results and provide the first demonstration that prostanoid tone in isolated guinea pig trachea is dependent on COX-2 activity. The results also suggest that the activity of indomethacin in this preparation is likely related to COX-2 inhibition.Key words: cyclooxygenase 2, relaxation, guinea pig trachea, cyclooxygenase 1.

Role of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) derived prostaglandins (PG) in adaptive cytoprotection induced by mild stress

1998 ◽  
Vol 114 ◽  
pp. A82
Author(s):  
T. Brzozowski ◽  
P.C. Konturek ◽  
R. Pajdo ◽  
N. Nagraba ◽  
A. Szczeklik ◽  
...  
Keyword(s):  
Cyclooxygenase 2 ◽  
Mild Stress ◽  
Adaptive Cytoprotection ◽  
Cyclooxygenase 1 ◽  
Cox 2 ◽  
Cox 1

Cyclooxygenases and prostaglandin E synthases in preimplantation mouse embryos

Zygote ◽  
2005 ◽  
Vol 13 (2) ◽  
pp. 103-108 ◽  
Author(s):  
Hui-Ning Tan ◽  
Ying Liu ◽  
Hong-Lu Diao ◽  
Zeng-Ming Yang
Keyword(s):  
Blastocyst Stage ◽  
Mouse Embryos ◽  
Prostaglandin E ◽  
Female Reproduction ◽  
Low Level ◽  
Preimplantation Mouse Embryos ◽  
Preimplantation Mouse ◽  
Cox 2 ◽  
High Level ◽  
Cox 1

Prostaglandin E2 (PGE2) is shown to be essential for female reproduction. Cyclooxygenase (COX) is a rate-limiting enzyme in prostaglandin synthesis from arachidonic acid and exists in two isoforms: COX-1 and COX-2. Prostaglandin E synthase (PGES) is a terminal prostanoid synthase and can catalyse the isomerization of the COX product PGH2 to PGE2, including microsomal PGES-1 (mPGES-1), cytosolic PGES (cPGES) and mPGES-2. This study examined the protein expression of COX-1, COX-2, mPGES-1, cPGES and mPGES-2 in preimplantation mouse embryos by immunohistochemistry. Embryos at different stages collected from oviducts or uteri were transferred into a flushed oviduct of non-pregnant mice. The oviducts containing embryos were paraffin-embedded and processed for immunostaining. COX-1 immunostaining was at a basal level in zygotes and a low level at the 2-cell stage, reaching a high level from the 4-cell to blastocyst stage. COX-2 immunostaining was at a low level at the zygote stage and was maintained at a high level from the 2-cell to blastocyst stages. A low level of mPGES-1 immunostaining was observed from the zygote to 8-cell stages. The signal for mPGES-1 immunostaining became stronger at the morula stage and was strongly seen at the blastocyst stage. cPGES immunostaining was strongly observed in zygotes, 2-cell and 8-cell embryos. There was a slight decrease in cPGES immunostaining at the 4-cell, morula and blastocyst stages. mPGES-2 immunostaining was at a low level from the zygote to morula stages and at a high level at the blastocyst stage. We found that the COX-1, COX-2, mPGES-1, cPGES and mPGES-2 protein signals were all at a high level at the blastocyst stage. PGE2 produced during the preimplantation development may play roles during embryo transport and implantation.

Sulforaphane, a Chemopreventive Compound, Inhibits Cyclooxygenase-2 and Microsomal Prostaglandin E Synthase-1 Expression in Human HT-29 Colon Cancer Cells

2018 ◽  
Vol 206 (1-2) ◽  
pp. 46-53 ◽  
Author(s):  
Maryam Sadat Tafakh ◽  
Massoud Saidijam ◽  
Tayebeh Ranjbarnejad ◽  
Sara Malih ◽  
Solmaz Mirzamohammadi ◽  
...  
Keyword(s):  
Anticancer Agents ◽  
Caspase 3 ◽  
Mrna Level ◽  
Cyclooxygenase 2 ◽  
Prostaglandin E ◽  
Prostaglandin E Synthase ◽  
Cox 2 ◽  
Ht 29 ◽  
Microsomal Prostaglandin E Synthase

Background: A high expression of prostaglandin E2 (PGE2) is found in colorectal cancer. Therefore, blocking of PGE2 generation has been identified as a promising approach for anticancer therapy. Sulforaphane (SFN), an isothiocyanate derived from glucosinolate, is used as the antioxidant and anticancer agents. Methods: HT-29 cells were treated with various concentrations of SFN and compared to untreated cells for the expression of microsomal prostaglandin E synthase-1 (mPGES-1), cyclooxygenase 2 (COX-2), hypoxia-inducible factor-1 (HIF-1), C-X-C chemokine receptor type 4 (CXCR4), vascular endothelial growth factor (VEGF), and matrix metalloproteinase (MMP)-2 and MMP-9 at the mRNA level. The PGE2 level was measured by ELISA assay. Apoptosis was evaluated by the proportion of sub-G1 cells. The activity of caspase-3 was determined using an enzymatic assay. HT-29 cell migration was assessed using a scratch test. Results: SFN preconditioning decreased the expression of COX-2, mPGES-1, HIF-1, VEGF, CXCR4, MMP-2, and MMP-9. An apoptotic effect of SFN was preceded by the activation of caspase-3 as well as accumulation of cells in the sub-G1 phase of the cell cycle. SFN decreased PGE2 generation and inhibited the in vitro motility/wound-healing activity of HT-29 cells. Conclusions: SFN anticancer effects are associated with antiproliferative, antiangiogenic, and antimetastatic activities arising from the downregulation of the COX-2/ mPGES-1 axis.

A role for cyclooxygenase-2 in lipopolysaccharide-induced anorexia in rats

2002 ◽  
Vol 283 (4) ◽  
pp. R862-R868 ◽  
Author(s):  
F. Lugarini ◽  
B. J. Hrupka ◽  
G. J. Schwartz ◽  
C. R. Plata-Salaman ◽  
W. Langhans
Keyword(s):  
Cerebrospinal Fluid ◽  
Cyclooxygenase 2 ◽  
Major Metabolite ◽  
Time Dependent ◽  
Selective Inhibitors ◽  
Cox 2 ◽  
Cox 1

Because nonselective cycloooxygenase (COX) inhibition attenuated anorexia after lipopolysaccharide (LPS) administration, we tested the ability of resveratrol (2.5, 10, and 40 mg/kg) and NS-398 (2.5, 10, and 40 mg/kg), selective inhibitors of the two COX isoforms COX-1 and -2, respectively, to attenuate LPS (100 μg/kg ip)-induced anorexia. NS-398 (10 and 40 mg/kg) administered with LPS at lights out attenuated LPS-induced anorexia, whereas resveratrol at all doses tested did not. Because prostaglandin (PG) E2 is considered the major metabolite synthesized by COX, we measured plasma and cerebrospinal fluid (CSF) PGE2levels after LPS administration. LPS induced a time-dependent increase of PGE2 in CSF but not in plasma. NS-398 (5, 10, and 40 mg/kg) blocked the LPS-induced increase in CSF PGE2, whereas resveratrol (10 mg/kg) did not. These results support a role of COX-2 in mediating the anorectic response to peripheral LPS and point at PGE2 as a potential neuromodulator involved in this response.

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