Regulation of prostaglandin biosynthesis in vivo by glutathione

Intraperitoneal administration of urate crystals to mice reduced subsequent macrophage conversion of arachidonic acid (AA) to prostaglandins (PGs) and 12-hydroxyeicosatetraenoic acid for up to 6 h. In contrast, levels of 12-hydroxyheptadecatrienoic acid (12-HHT) were markedly elevated. This metabolic profile was previously observed in vitro when recombinant cyclooxygenase (COX) enzymes were incubated with reduced glutathione (GSH). Analysis of peritoneal GSH levels revealed a fivefold elevation after urate crystal administration. The GSH synthesis inhibitorl-buthionine-[ S, R]-sulfoximine partially reversed the urate crystal effect on both GSH elevation and PG synthesis. Moreover, addition of exogenous GSH to isolated peritoneal macrophages shifted AA metabolism from PGs to 12-HHT. Urate crystal administration reduced COX-1, but induced COX-2 expression in peritoneal cells. The reduction of COX-1 may contribute to the attenuation of PG synthesis after 1 and 2 h, but PG synthesis remained inhibited up to 6 h, when COX-2 levels were high. Overall, our results indicate that elevated GSH levels inhibit PG production in this model and provide in vivo evidence for the role of GSH in the regulation of PG biosynthesis.

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The Role of Propolis in Pulp Pain by Inhibiting Cyclooxygenase-2 Expression

Conservative Dentistry Journal ◽

10.20473/cdj.v11i1.2021.11-18 ◽

2021 ◽

Vol 11 (1) ◽

pp. 11

Author(s):

Ira Widjiastuti ◽

Widya Saraswati ◽

Annisa Rahma

Keyword(s):

Side Effects ◽

Pain Relief ◽

Inflammatory Pain ◽

Cyclooxygenase 2 ◽

Propolis Extract ◽

In Silico Studies ◽

Cox 2

Background: Inflammation of the pulp can lead to elicit pain. Pain in inflammation is induced by the cyclooxygenase-2 enzyme (COX-2) which induces prostaglandin E2 (PGE2) resulting in pain. Pain in the pulp can be relieved by eugenol. In its application, eugenol is toxic to pulp fibroblasts. Due to the side effect, it is worth considering other biocompatible materials with minimal side effects, such as propolis. Flavonoids and phenolic acids that contained in propolis can inhibit COX-2. Therefore, an analysis outlined in the literature review is needed to examine the results of research related to the role of propolis as pulp pain relief by inhibiting COX-2 expression. Purpose: To analyze the role of propolis in pulp pain by inhibiting COX-2 expression. Reviews: Propolis extract that extracted by ethanol, water, and hydroalcohol has pain relief properties in the pulp by inhibiting COX-2 by directly binding to the COX-2 receptors and by reducing the production of proinflammatory cytokines which are COX-2 inducers, proven through in vivo, in vitro, and in silico studies in various target cell organs. Conclusion: Propolis extract has high prospect as inflammatory pain inhibitor in the pulp by inhibit COX-2 expression.

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A Critical Role of Activin A in Maturation of Mouse Peritoneal Macrophages in vitro and in vivo

Cellular and Molecular Immunology ◽

10.1038/cmi.2009.50 ◽

2009 ◽

Vol 6 (5) ◽

pp. 387-392 ◽

Cited By ~ 27

Author(s):

Yinan Wang ◽

Xueling Cui ◽

Guixiang Tai ◽

Jingyan Ge ◽

Nan Li ◽

...

Keyword(s):

Critical Role ◽

Peritoneal Macrophages ◽

Activin A ◽

Mouse Peritoneal Macrophages

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Coordinate expression of secretory phospholipase A2 and cyclooxygenase-2 in activated human keratinocytes

AJP Cell Physiology ◽

10.1152/ajpcell.2000.278.4.c822 ◽

2000 ◽

Vol 278 (4) ◽

pp. C822-C833 ◽

Cited By ~ 34

Author(s):

Krystyna E. Rys-Sikora ◽

Raymond L. Konger ◽

John W. Schoggins ◽

Rama Malaviya ◽

Alice P. Pentland

Keyword(s):

Wound Repair ◽

Human Keratinocytes ◽

Plating Density ◽

Coordinate Expression ◽

Cox 2 ◽

Type V ◽

In Vitro Wounding

PGE2 levels are altered in human epidermis after in vivo wounding; however, mechanisms modulating PGE2 production in activated keratinocytes are unclear. In previous studies, we showed that PGE2 is a growth-promoting autacoid in human primary keratinocyte cultures, and its production is modulated by plating density, suggesting that regulated PGE2 synthesis is an important component of wound healing. Here, we examine the role of phospholipase A2(PLA2) and cyclooxygenase (COX) enzymes in modulation of PGE2 production. We report that the increased PGE2 production that occurs in keratinocytes grown in nonconfluent conditions is also observed after in vitro wounding, indicating that similar mechanisms are involved. This increase was associated with coordinate upregulation of both COX-2 and secretory PLA2 (sPLA2) proteins. Increased sPLA2 activity was also observed. By RT-PCR, we identified the presence of type IIA and type V sPLA2, along with the M-type sPLA2 receptor. Thus the coordinate expression of sPLA2 and COX-2 may be responsible for the increased prostaglandin synthesis in activated keratinocytes during wound repair.

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Anti-inflammatory Effects of Cavidine In Vitro and In Vivo, a Selective COX-2 Inhibitor in LPS-Induced Peritoneal Macrophages of Mouse

Inflammation ◽

10.1007/s10753-014-0054-4 ◽

2014 ◽

Vol 38 (2) ◽

pp. 923-933 ◽

Cited By ~ 12

Author(s):

Xiaofeng Niu ◽

Hailin Zhang ◽

Weifeng Li ◽

Qingli Mu ◽

Huan Yao ◽

...

Keyword(s):

Peritoneal Macrophages ◽

Cox 2 ◽

Anti Inflammatory

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Are there attacking points in the eicosanoid cascade for chemotherapeutic options in benign meningiomas?

Neurosurgical FOCUS ◽

10.3171/foc-07/10/e8 ◽

2007 ◽

Vol 23 (4) ◽

pp. E8 ◽

Cited By ~ 4

Author(s):

Christina Pfister ◽

Rainer Ritz ◽

Heike Pfrommer ◽

Antje Bornemann ◽

Marcos S. Tatagiba ◽

...

Keyword(s):

World Health ◽

Pcr Analysis ◽

Prostaglandin E ◽

Tissue Samples ◽

Human Cortex ◽

Normal Human ◽

Cox 2 ◽

Cox 1

Object The current treatment for recurrent or malignant meningiomas with adjuvant therapies has not been satisfactory, and there is an intense interest in evaluating new molecular markers to act as therapeutic targets. Enzymes of the arachidonic acid (AA) cascade such as cyclooxygenase (COX)–2 or 5-lipoxygenase (5-LO) are upregulated in a number of epithelial tumors, but to date there are hardly any data about the expression of these markers in meningiomas. To find possible targets for chemotherapeutic intervention, the authors evaluated the expression of AA derivatives at different molecular levels in meningiomas. Methods One hundred and twenty-four meningioma surgical specimens and normal human cortical tissue samples were immunohistochemically and cytochemically stained for COX-2, COX-1, 5-LO, and prostaglandin E receptor 4 (PTGER4). In addition, Western blot and polymerase chain reaction (PCR) analyses were performed to detect the presence of eicosanoids in vivo and in vitro. Results Sixty (63%) of 95 benign meningiomas, 21 (88%) of 24 atypical meningiomas, all five malignant meningiomas, and all normal human cortex samples displayed high COX-2 immunoreactivity. All cultured specimens and IOMM-Lee cells stained positive for COX-2, COX-1, 5-LO, and PTGER4. The PCR analysis demonstrated no changes in eicosanoid expression among meningiomas of different World Health Organization grades and in normal human cortical and dura mater tissue. Conclusions Eicosanoid derivatives COX-1, COX-2, 5-LO, and PTGER4 enzymes show a high universal expression in meningiomas but are not upregulated in normal human cortex and dura tissue. This finding of the ubiquitous presence of these enzymes in meningiomas offers an excellent baseline for testing upcoming chemotherapeutic treatments.

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The Immunomodulatory Effects of AlbuminIn VitroandIn Vivo

Advances in Pharmacological Sciences ◽

10.1155/2011/691928 ◽

2011 ◽

Vol 2011 ◽

pp. 1-7 ◽

Cited By ~ 3

Author(s):

Derek S. Wheeler ◽

John S. Giuliano ◽

Patrick M. Lahni ◽

Alvin Denenberg ◽

Hector R. Wong ◽

...

Keyword(s):

Gene Expression ◽

Lethal Dose ◽

Intraperitoneal Administration ◽

Peritoneal Macrophages ◽

Luciferase Reporter Assay ◽

Luciferase Reporter ◽

Reporter Assay ◽

Dose Dependent

Albumin appears to have proinflammatory effectsin vitro. We hypothesized that albumin would induce a state of tolerance to subsequent administration of lipopolysaccharide (LPS)in vitroandin vivo. RAW264.7 and primary peritoneal macrophages were treated with increasing doses of bovine serum albumin (BSA) and harvested for NF-κB luciferase reporter assay or TNF-αELISA. In separate experiments, RAW264.7 cells were preconditioned with 1 mg/mL BSA for 18 h prior to LPS (10 μg/mL) treatment and harvested for NF-κB luciferase reporter assay or TNF-αELISA. Finally, C57Bl/6 mice were preconditioned with albumin via intraperitoneal administration 18 h prior to a lethal dose of LPS (60 mg/kg body wt). Blood was collected at 6 h after LPS administration for TNF-αELISA. Albumin produced a dose-dependent and TLR-4-dependent increase in NF-κB activation and TNF-αgene expressionin vitro. Albumin preconditioning abrogated the LPS-mediated increase in NF-κB activation and TNF-αgene expressionin vitroandin vivo. The clinical significance of these findings remains to be elucidated.

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Increased cyclooxygenase-2 expression and prostaglandin E2production in pressurized renal medullary interstitial cells

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00544.2009 ◽

2010 ◽

Vol 299 (3) ◽

pp. R823-R831 ◽

Cited By ~ 16

Author(s):

Inge Carlsen ◽

Kaitlin E. Donohue ◽

Anja M. Jensen ◽

Angela L. Selzer ◽

Jie Chen ◽

...

Keyword(s):

Mechanical Stress ◽

Ureteral Obstruction ◽

Interstitial Cells ◽

Inflammatory Stress ◽

Protein Levels ◽

Cox 2 ◽

Cox 1 ◽

Expression And Activity

Renal medullary interstitial cells (RMICs) are subjected to osmotic, inflammatory, and mechanical stress as a result of ureteral obstruction, which may influence the expression and activity of cyclooxygenase type 2 (COX-2). Inflammatory stress strongly induces COX-2 in RMICs. To explore the direct effect of mechanical stress on the expression and activity of COX-2, cultured RMICs were subjected to varying amounts of pressure over time using a novel pressure apparatus. COX-2 mRNA and protein were induced following 60 mmHg pressure for 4 and 6 h, respectively. COX-1 mRNA and protein levels were unchanged. PGE2production in the RMICs was increased when cells were subjected to 60 mmHg pressure for 6 h and was prevented by a selective COX-2 inhibitor. Pharmacological inhibition indicating that pressure-induced COX-2 expression is dependent on p38 MAPK and biochemical knockdown experiments showed that NF-κB might be involved in the COX-2 induction by pressure. Importantly, terminal deoxyneucleotidyl transferase-mediated dUTP nick-end labeling and methylthiazoletetetrazolium assay studies showed that subjecting RMICs to 60 mmHg pressure for 6 h does not affect cell viability, apoptosis, and proliferation. To further examine the regulation of COX-2 in vivo, rats were subjected to unilateral ureteral obstruction (UUO) for 6 and 12 h. COX-2 mRNA and protein level was increased in inner medulla in response to 6- and 12-h UUO. COX-1 mRNA and protein levels were unchanged. These findings suggest that in vitro application of pressure recapitulates the effects on RMICs found after in vivo UUO. This directly implicates pressure as an important regulator of renal COX-2 expression.

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COX-2 mediates angiotensin II-induced (pro)renin receptor expression in the rat renal medulla

AJP Renal Physiology ◽

10.1152/ajprenal.00548.2013 ◽

2014 ◽

Vol 307 (1) ◽

pp. F25-F32 ◽

Cited By ~ 31

Author(s):

Fei Wang ◽

Xiaohan Lu ◽

Kexin Peng ◽

Li Zhou ◽

Chunling Li ◽

...

Keyword(s):

Angiotensin Ii ◽

Protein Expression ◽

Renal Medulla ◽

Receptor Expression ◽

Ang Ii ◽

Cox 2 ◽

Renin Content

(Pro)renin receptor (PRR) is predominantly expressed in the distal nephron where it is activated by angiotensin II (ANG II), resulting in increased renin activity in the renal medulla thereby amplifying the de novo generation and action of local ANG II. The goal of the present study was to test the role of cycloxygenase-2 (COX-2) in meditating ANG II-induced PRR expression in the renal medulla in vitro and in vivo. Exposure of primary rat inner medullary collecting duct cells to ANG II induced sequential increases in COX-2 and PRR protein expression. When the cells were pretreated with a COX-2 inhibitor NS-398, ANG II-induced upregulation of PRR protein expression was almost completely abolished, in parallel with the changes in medium active renin content. The inhibitory effect of NS-398 on the PRR expression was reversed by adding exogenous PGE2. A 14-day ANG II infusion elevated renal medullary PRR expression and active and total renin content in parallel with increased urinary renin, all of which were remarkably suppressed by the COX-2 inhibitor celecoxib. In contrast, plasma and renal cortical active and total renin content were suppressed by ANG II treatment, an effect that was unaffected by COX-2 inhibition. Systolic blood pressure was elevated with ANG II infusion, which was attenuated by the COX-2 inhibition. Overall, the results obtained from in vitro and in vivo studies established a crucial role of COX-2 in mediating upregulation of renal medullary PRR expression and renin content during ANG II hypertension.

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Perspective of strategic plasma therapy for prognostic improvement of patients with ovarian cancer

MRS Proceedings ◽

10.1557/opl.2013.1188 ◽

2013 ◽

Vol 1598 ◽

Author(s):

Hiroaki Kajiyama ◽

Fumi Utsumi ◽

Kae Nakamura ◽

Hiromasa Tanaka ◽

Masaru Hori ◽

...

Keyword(s):

Atmospheric Pressure ◽

Antitumor Effect ◽

Intraperitoneal Administration ◽

Atmospheric Pressure Plasma ◽

Plasma Therapy ◽

Intracellular Mechanism ◽

Patients Experience

ABSTRACTEpithelial ovarian carcinoma (EOC) is the leading cause of cancer-related death in women in Western countries. Once patients experience recurrence, complete cure is almost impossible. We elucidated the effect of nonequilibrium atmospheric pressure plasma on the growth of EOC, particularly in plasma-activated medium (PAM). Furthermore, we examined the role of reactive oxygen species (ROS) or their scavengers in chronic antineoplastic-resistant EOC cells. As a result, we showed PAM induced the antitumor effect of EOC cells in vitro and in vivo, even in chemoresistant cells. To apply the plasma treatment for advanced or recurrent EOC, we suggest adopting indirect plasma therapy instead of direct plasma considering intraperitoneal administration in the future. However, there are several problems under investigation, including intracellular mechanism of antitumor effect by PAM and adverse event in vivo.

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