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

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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The role of the interferon regulatory factors, IRF-1 and IRF-2, in LPS-induced cyclooxygenase-2 (COX-2) expression in vivo and in vitro

Journal of Endotoxin Research ◽

10.1177/09680519020080050101 ◽

2002 ◽

Vol 8 (5) ◽

pp. 381-390 ◽

Cited By ~ 2

Author(s):

Shuling Zhang ◽

Karen Thomas ◽

Jorge C.G. Blanco ◽

Cindy A. Salkowski ◽

Stefanie N. Vogel

Keyword(s):

Cyclooxygenase 2 ◽

Regulatory Factors ◽

Interferon Regulatory Factors ◽

Cox 2

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The role of the interferon regulatory factors, IRF-1 and IRF-2, in LPS-induced cyclooxygenase-2 (COX-2) expression in vivo and in vitro

CrossRef Listing of Deleted DOIs ◽

10.1179/096805102125000713 ◽

2002 ◽

Vol 8 (5) ◽

pp. 379-388 ◽

Cited By ~ 9

Author(s):

Shuling Zhang ◽

Karen Thomas ◽

Jorge C. G. Blanco ◽

Cindy A. Salkowski ◽

Stefanie N. Vogel

Keyword(s):

Cyclooxygenase 2 ◽

Regulatory Factors ◽

Interferon Regulatory Factors ◽

Cox 2

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Induction of Cyclooxygenase 2 by Streptococcus pyogenes Is Mediated by Cytolysins

Journal of Innate Immunity ◽

10.1159/000479153 ◽

2017 ◽

Vol 9 (6) ◽

pp. 587-597 ◽

Cited By ~ 4

Author(s):

Ulrike Blaschke ◽

Andreas Beineke ◽

Johanna Klemens ◽

Eva Medina ◽

Oliver Goldmann

Keyword(s):

Streptococcus Pyogenes ◽

Cyclooxygenase 2 ◽

Arachidonic Acid Metabolite ◽

Infection Model ◽

Synergistic Activity ◽

Wild Type ◽

Cox 2

Prostaglandin E2 (PGE2), an arachidonic acid metabolite regulating a broad range of physiological activities, is an important modulator of the severity of infection caused by Streptococcus pyogenes. Here, we investigated the role of streptococcal cytolysin S (SLS) and streptococcal cytolysin O (SLO) in the induction of cyclooxygenase-2 (COX-2), the rate-limiting enzyme in the synthesis of prostaglandins, in in vitro cultured macrophages and during in vivo infection. Macrophages were infected with S. pyogenes wild type or with the isogenic mutant strains deficient in SLS (ΔSLS), SLO (ΔSLO), or both (ΔSLS/ΔSLO), and the expression of COX-2 was determined at the transcriptional and the protein level. The results indicated that S. pyogenes induced expression of COX-2 and concomitant synthesis of PGE2 in macrophages mediated by the synergistic activity of both SLS and SLO, and involved calcium and the PKC/JNK signaling pathway. These results were validated using recombinant cytolysins. In a murine skin infection model, COX-2-positive cells were found more abundant at the site of S. pyogenes wild-type infection than at the site of infection with ΔSLS/ΔSLO mutant strain. These findings suggest that inhibitory targeting of SLS and SLO could ameliorate the adverse effects of high levels of prostaglandins during S. pyogenes infection.

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MESUAFERRIN A-BIOACTIVE FLAVONOID ISOLATED FROM THE BARK OF MESUA FERREA L. AGAINST PHOSPHOLIPASE A2, CYCLOOXYGENASE AND LIPOXYGENASE: AN IN VITRO, IN VIVO AND IN SILICO APPROACH

International Journal of Pharmacy and Pharmaceutical Sciences ◽

10.22159/ijpps.2018v10i2.23576 ◽

2018 ◽

Vol 10 (2) ◽

pp. 102

Author(s):

Krishna Chaithanya K. ◽

Gopalakrishnan V. K. ◽

Zenebe Hagos ◽

Govinda Rao D.

Keyword(s):

Inhibitory Activity ◽

In Silico ◽

Late Phase ◽

Paw Edema ◽

Dual Inhibitor ◽

Metabolizing Enzymes ◽

In Silico Studies ◽

Cox 2

Objective: The main objective of the present study was to evaluate the anti-inflammatory activity of isolated bioactive flavonoid Mesuaferrin-A from the bark of Mesuaferrea L. by in vitro, in vivo and in silico approach.Methods: To evaluate the effect of isolated bioactive flavonoid Mesuaferrin-A on arachidonic acid metabolizing enzymes (PLA2, COX-2 and 5-LOX) using in vitro methods, followed by carrageenan-induced paw edema model by in vivo and to determine the binding orientation and interactions of Mesuaferrin-A onarachidonic acid metabolizing enzymes (PLA2, COX-2 and 5-LOX) crystal proteins using molecular docking (in silico) studies.Results: Mesuaferrin-A exhibited a dose-dependent significant 5-LOX inhibitory and considerable COX-2 inhibitory activity by in vitro, The inhibitory activities of 5-LOX and COX-2 at 100µg/ml were found to be 78.67%, 81.03% with IC50 values of 45.22µg/ml and 35.74µg/ml respectively. Whereas Mesuaferrin-A showed less PLA2 inhibitory activity. Mesuaferrin-A showed 68.34% inhibitory activity at 400 mg/kg body weight at the late phase of carrageenan-induced paw edema, and In silico studies demonstrated that Mesuaferrin-A strongly binds with 5-LOX and COX-2, these strong binding affinity of Mesuaferrin-A on active site amino acids of 5-LOX and COX-2 may be responsible for inhibition of enzyme activity. Mesuaferrin-A showeda comparable 5-LOX and COX-2 inhibition activity with (positive control).Conclusion: It was concluded that Mesuaferrin-A act as 5-LOX and COX dual inhibitor, from the results it was suggests that Mesuaferrin-A, may be an effective preventive and therapeutic approach for patients with inflammatory-related diseases.

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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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Radiosynthesis of a 18F-labeled 2,3-diarylsubstituted indole via McMurry coupling for functional characterization of cyclooxygenase-2 (COX-2) in vitro and in vivo

Bioorganic & Medicinal Chemistry ◽

10.1016/j.bmc.2012.04.022 ◽

2012 ◽

Vol 20 (11) ◽

pp. 3410-3421 ◽

Cited By ~ 29

Author(s):

Torsten Kniess ◽

Markus Laube ◽

Ralf Bergmann ◽

Fabian Sehn ◽

Franziska Graf ◽

...

Keyword(s):

Functional Characterization ◽

Cyclooxygenase 2 ◽

Cox 2

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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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Cyclosporin A impairs dendritic cell migration by regulating chemokine receptor expression and inhibiting cyclooxygenase-2 expression

Blood ◽

10.1182/blood-2003-07-2412 ◽

2004 ◽

Vol 103 (2) ◽

pp. 413-421 ◽

Cited By ~ 91

Author(s):

Taoyong Chen ◽

Jun Guo ◽

Mingjin Yang ◽

Chaofeng Han ◽

Minghui Zhang ◽

...

Keyword(s):

Cyclosporin A ◽

Chemokine Receptor ◽

Cyclooxygenase 2 ◽

Lymphoid Organs ◽

Receptor Expression ◽

Chemokine Receptor Expression ◽

Cox 2 ◽

Secondary Lymphoid Organs

Abstract Migration of dendritic cells (DCs) into tissues and secondary lymphoid organs plays a crucial role in the initiation of innate and adaptive immunity. In this article, we show that cyclosporin A (CsA) impairs the migration of DCs both in vitro and in vivo. Exposure of DCs to clinical concentrations of CsA neither induces apoptosis nor alters development but does impair cytokine secretion, chemokine receptor expression, and migration. In vitro, CsA impairs the migration of mouse bone marrow–derived DCs toward macrophage inflammatory protein-3β (MIP-3β) and induces them to retain responsiveness to MIP-1α after lipopolysaccharide (LPS)–stimulated DC maturation, while in vivo administration of CsA inhibits the migration of DCs out of skin and into the secondary lymphoid organs. CsA impairs chemokine receptor and cyclooxygenase-2 (COX-2) expression normally triggered in LPS-stimulated DCs; administration of exogenous prostaglandin E2 (PGE2) reverses the effects of CsA on chemokine receptor expression and DC migration. Inhibition of nuclear factor–κB (NF-κB) and mitogen-activated protein kinase (MAPK) pathway signaling by CsA may be responsible for the CsA-mediated effects on the regulation of chemokine receptor and cyclooxygenase-2 (COX-2) expression. Impairment of DC migration due to inhibition of PGE2 production and regulation of chemokine receptor expression may contribute, in part, to CsA-mediated immunosuppression.

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Cross-talk between SIM2s and NFκB regulates cyclooxygenase 2 expression in breast cancer

Breast Cancer Research ◽

10.1186/s13058-019-1224-y ◽

2019 ◽

Vol 21 (1) ◽

Cited By ~ 2

Author(s):

Garhett L. Wyatt ◽

Lyndsey S. Crump ◽

Chloe M. Young ◽

Veronica M. Wessells ◽

Cole M. McQueen ◽

...

Keyword(s):

Breast Cancer ◽

Cyclooxygenase 2 ◽

Luciferase Reporter ◽

Signaling Proteins ◽

Dependent Manner ◽

Mcf7 Cells ◽

Human Breast Carcinomas ◽

Cox 2

Abstract Background Breast cancer is a leading cause of cancer-related death for women in the USA. Thus, there is an increasing need to investigate novel prognostic markers and therapeutic methods. Inflammation raises challenges in treating and preventing the spread of breast cancer. Specifically, the nuclear factor kappa b (NFκB) pathway contributes to cancer progression by stimulating proliferation and preventing apoptosis. One target gene of this pathway is PTGS2, which encodes for cyclooxygenase 2 (COX-2) and is upregulated in 40% of human breast carcinomas. COX-2 is an enzyme involved in the production of prostaglandins, which mediate inflammation. Here, we investigate the effect of Singleminded-2s (SIM2s), a transcriptional tumor suppressor that is implicated in inhibition of tumor growth and metastasis, in regulating NFκB signaling and COX-2. Methods For in vitro experiments, reporter luciferase assays were utilized in MCF7 cells to investigate promoter activity of NFκB and SIM2. Real-time PCR, immunoblotting, immunohistochemistry, and chromatin immunoprecipitation assays were performed in SUM159 and MCF7 cells. For in vivo experiments, MCF10DCIS.COM cells stably expressing SIM2s-FLAG or shPTGS2 were injected into SCID mice and subsequent tumors harvested for immunostaining and analysis. Results Our results reveal that SIM2 attenuates the activation of NFκB as measured using NFκB-luciferase reporter assay. Furthermore, immunostaining of lysates from breast cancer cells overexpressing SIM2s showed reduction in various NFκB signaling proteins, as well as pAkt, whereas knockdown of SIM2 revealed increases in NFκB signaling proteins and pAkt. Additionally, we show that NFκB signaling can act in a reciprocal manner to decrease expression of SIM2s. Likewise, suppressing NFκB translocation in DCIS.COM cells increased SIM2s expression. We also found that NFκB/p65 represses SIM2 in a dose-dependent manner, and when NFκB is suppressed, the effect on the SIM2 is negated. Additionally, our ChIP analysis confirms that NFκB/p65 binds directly to SIM2 promoter site and that the NFκB sites in the SIM2 promoter are required for NFκB-mediated suppression of SIM2s. Finally, overexpression of SIM2s decreases PTGS2 in vitro, and COX-2 staining in vivo while decreasing PTGS2 and/or COX-2 activity results in re-expression of SIM2. Conclusion Our findings identify a novel role for SIM2s in NFκB signaling and COX-2 expression.

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