scholarly journals Orally Administered Phlorotannins from Eisenia arborea Suppress Chemical Mediator Release and Cyclooxygenase-2 Signaling to Alleviate Mouse Ear Swelling

Marine Drugs ◽  
2018 ◽  
Vol 16 (8) ◽  
pp. 267 ◽  
Author(s):  
Yoshimasa Sugiura ◽  
Masakatsu Usui ◽  
Hirotaka Katsuzaki ◽  
Kunio Imai ◽  
Makoto Kakinuma ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Cell Model ◽  
Cyclooxygenase 2 ◽  
Mediator Release ◽  
Chemical Mediator ◽  
Eisenia Arborea ◽  
Mouse Ear ◽  
Cox 2 ◽  
Suppression Effects

Phlorotannin is the collective term for polyphenols derived from brown algae belonging to the genera Ascopyllum, Ecklonia, Eisenia, Fucus and Sargassum etc. Since the incidence of allergies is currently increasing in the world, there is a focus on phlorotannins having anti-allergic and anti-inflammatory effects. In this study, six purified phlorotannins (eckol; 6,6′-bieckol; 6,8′-bieckol; 8,8′-bieckol; phlorofucofuroeckol (PFF)-A and PFF-B) from Eisenia arborea, orally administered to mice, were examined for their suppression effects on ear swelling. In considering the suppression, we also examined whether the phlorotannins suppressed release of chemical mediators (histamine, leukotriene B4 and prostaglandin E2), and mRNA expression and/or the activity of cyclooxygenase-2 (COX-2), using RBL-2H3 cells, a cultured mast cell model. Results showed that the phlorotnannins exhibited suppression effects in all experiments, with 6,8′-bieckol, 8,8′-bieckol and PFF-A showing the strongest of these effects. In conclusion, orally administered phlorotannins suppress mouse ear swelling, and this mechanism apparently involves suppression of chemical mediator release and COX-2 mRNA expression or activity. This is the first report of the anti-allergic effects of the orally administered purified phlorotannins in vivo. Phlorotannins show potential for use in functional foods or drugs.

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

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.

scholarly journals Bakuchiol Suppresses Inflammatory Responses Via the Downregulation of the p38 MAPK/ERK Signaling Pathway

2019 ◽  
Vol 20 (14) ◽  
pp. 3574 ◽  
Author(s):  
Hye-Sun Lim ◽  
Yu Jin Kim ◽  
Bu-Yeo Kim ◽  
Soo-Jin Jeong
Keyword(s):  
Mrna Expression ◽  
P38 Mapk ◽  
Inflammatory Responses ◽  
Mitogen Activated Protein Kinase ◽  
Enzyme Linked Immunosorbent Assay ◽  
Mice Model ◽  
Tnf Α ◽  
Cox 2

The purpose of the present study was to evaluate the effects of bakuchiol on the inflammatory response and to identify the molecular mechanism of the inflammatory effects in a lipopolysaccharide (LPS)-stimulated BV-2 mouse microglial cell line and mice model. The production of prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) was measured by enzyme-linked immunosorbent assay. The mRNA expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), TNF-α, and IL-6 was measured using reverse transcription–polymerase chain reaction analysis. Mitogen-activated protein kinase (MAPK) phosphorylation was determined by western blot analysis. In vitro experiments, bakuchiol significantly suppressed the production of PGE2 and IL-6 in LPS-stimulated BV-2 cells, without causing cytotoxicity. In parallel, bakuchiol significantly inhibited the LPS-stimulated expression of iNOS, COX-2, and IL-6 in BV-2 cells. However, bakuchiol had no effect on the LPS-stimulated production and mRNA expression of TNF-α or on LPS-stimulated c-Jun NH2-terminal kinase phosphorylation. In contrast, p38 MAPK and extracellular signal-regulated kinase (ERK) phosphorylation were inhibited by bakuchiol. In vivo experiments, Bakuchiol reduced microglial activation in the hippocampus and cortex tissue of LPS-injected mice. Bakuchiol significantly suppressed LPS-injected production of TNF-α and IL-6 in serum. These results indicate that the anti-neuroinflammatory effects of bakuchiol in activated microglia are mainly regulated by the inhibition of the p38 MAPK and ERK pathways. We suggest that bakuchiol may be beneficial for various neuroinflammatory diseases.

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

2012 ◽  
Vol 20 (11) ◽  
pp. 3410-3421 ◽  
Author(s):  
Torsten Kniess ◽  
Markus Laube ◽  
Ralf Bergmann ◽  
Fabian Sehn ◽  
Franziska Graf ◽  
...  
Keyword(s):  
Functional Characterization ◽  
Cyclooxygenase 2 ◽  
Cox 2

scholarly journals Cyclooxygenase-2 (COX-2) mRNA Expression Levels in Normal Lung Tissues and Non-small Cell Lung Cancers

1999 ◽  
Vol 90 (12) ◽  
pp. 1338-1373 ◽  
Author(s):  
Mari Ochiai ◽  
Tetsuya Oguri ◽  
Takeshi Isobe ◽  
Shinichi Ishioka ◽  
Michio Yamakido
Keyword(s):  
Mrna Expression ◽  
Small Cell ◽  
Cyclooxygenase 2 ◽  
Normal Lung ◽  
Small Cell Lung ◽  
Lung Cancers ◽  
Expression Levels ◽  
Cox 2 ◽  
Mrna Expression Levels

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

Blood ◽  
2004 ◽  
Vol 103 (2) ◽  
pp. 413-421 ◽  
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.

Fragile X-related protein 1 (FXR1) regulates cyclooxygenase-2 (COX-2) expression at the maternal–fetal interface

2018 ◽  
Vol 30 (11) ◽  
pp. 1566 ◽  
Author(s):  
Xiao-Cui Li ◽  
Meng-fan Song ◽  
Feng Sun ◽  
Fu-Ju Tian ◽  
Yu-mei Wang ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Recurrent Miscarriage ◽  
Fragile X ◽  
Firefly Luciferase ◽  
Cyclooxygenase 2 ◽  
Luciferase Reporter ◽  
Related Protein ◽  
Expression Levels ◽  
Cox 2 ◽  
Mrna Expression Levels

Cyclooxygenase-2 (COX-2) is regulated post-transcriptionally by the AU-rich element (ARE) in the 3′-untranslated region (UTR) of its mRNA. However, the mechanism of COX-2 induction in infertility has not been thoroughly elucidated to date. The aim of this study was to examine the association between COX-2 and fragile X-related protein 1 (FXR1) in trophoblasts. Using quantitative reverse transcription polymerase chain reaction, our results showed that FXR1 mRNA expression levels were significantly decreased in trophoblasts from recurrent miscarriage patients compared with healthy controls; conversely, COX-2 mRNA expression levels were increased in patient samples. We also observed that FXR1 was highly expressed in human placental villi during early pregnancy. Furthermore, we used western blotting and immunofluorescence to analyse the expression levels of FXR1 and COX-2 in HTR-8 cells that were treated with tumour necrosis factor α; we observed that the expression of COX-2 was clearly increased in HTR-8 cells treated with FXR1 small interfering RNA, whereas the expression of COX-2 was effectively decreased in HTR-8 cells with FXR1 overexpressed via a plasmid. Importantly, bioinformatics analysis identified FXR1 binding sites in the 3′-UTR region of COX-2 and firefly luciferase reporter assay analysis verified that FXR1 binds directly to the 3′-UTR region of COX-2. ELISA assays showed that overexpression of FXR1 enhanced vascular endothelial growth factor-A and interleukin-8 expression in HTR-8 cells, whereas conversely, knockdown of FXR1 effectively repressed these effects. In conclusion, the results of this study indicate that FXR1 is a novel COX-2 regulatory factor.

scholarly journals IVIVC Assessment of Two Mouse Brain Endothelial Cell Models for Drug Screening

Pharmaceutics ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 587 ◽  
Author(s):  
Ina Puscas ◽  
Florian Bernard-Patrzynski ◽  
Martin Jutras ◽  
Marc-André Lécuyer ◽  
Lyne Bourbonnière ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Mrna Expression ◽  
Mouse Brain ◽  
Drug Screening ◽  
Cell Model ◽  
Drug Permeability ◽  
Mouse Brain Endothelial Cells ◽  
Primary Model

Since most preclinical drug permeability assays across the blood-brain barrier (BBB) are still evaluated in rodents, we compared an in vitro mouse primary endothelial cell model to the mouse b.End3 and the acellular parallel artificial membrane permeability assay (PAMPA) models for drug screening purposes. The mRNA expression of key feature membrane proteins of primary and bEnd.3 mouse brain endothelial cells were compared. Transwell® monolayer models were further characterized in terms of tightness and integrity. The in vitro in vivo correlation (IVIVC) was obtained by the correlation of the in vitro permeability data with log BB values obtained in mice for seven drugs. The mouse primary model showed higher monolayer integrity and levels of mRNA expression of BBB tight junction (TJ) proteins and membrane transporters (MBRT), especially for the efflux transporter Pgp. The IVIVC and drug ranking underlined the superiority of the primary model (r2 = 0.765) when compared to the PAMPA-BBB (r2 = 0.391) and bEnd.3 cell line (r2 = 0.019) models. The primary monolayer mouse model came out as a simple and reliable candidate for the prediction of drug permeability across the BBB. This model encompasses a rapid set-up, a fair reproduction of BBB tissue characteristics, and an accurate drug screening.

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

2019 ◽  
Vol 21 (1) ◽  
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.

253 GENE SILENCING OF CYCLOOXYGENASE-2 mRNA BY RNA INTERFERENCE IN BOVINE CUMULUS - GRANULOSA CELLS

2006 ◽  
Vol 18 (2) ◽  
pp. 234
Author(s):  
S.-I. Kobayashi ◽  
M. Sakatani ◽  
S. Kobayashi ◽  
K. Okuda ◽  
M. Takahashi
Keyword(s):  
Gene Expression ◽  
Gene Silencing ◽  
Mrna Expression ◽  
Culture Medium ◽  
Cyclooxygenase 2 ◽  
Target Cells ◽  
Specific Gene ◽  
Cox 2 ◽  
Sirna Group ◽  
Interference Rna

Recently, interference RNA (RNAi), inducing inhibition of the specific gene expression, attracted a lot of attention. Many researchers have reported that the 21-mer small interference RNA (siRNA) is introduced into target cells and then siRNA can suppress the gene expression. RNAi is a useful tool for functional analysis of specific genes. However, there is little information about RNAi for the analysis of gene function in reproductive physiology in ruminants. Thus, this study was aimed at evaluating RNAi for the analysis of cyclooxygenase-2 (Cox-2) mRNA expression in bovine cumulus-granulosa (CG) cells as well as prostaglandin F2� (PGF2�) production. We investigated both the effective concentration of Cox-2 siRNA and the effect of the introduction time of siRNA on Cox-2 mRNA expression. Bovine CG cells were collected at slaughterhouse and cultured in 4-well dishes. After the cells reached confluency, two experiments were conducted. In the present study, Cox-2 siRNA was simply added to culture medium with lipofectamine" 2000 (Invitrogen Japan K. K., Tokyo, Japan) as the transfection reagent. In experiment 1, the concentration of 0, 100, 250, and 500 pM of Cox-2 siRNA was introduced into the CG cells. After 24 h of introduction, the amount of mRNA expression for Cox-2 was measured by reverse transcription polymerase chain reaction (RT-PCR) and real-time PCR. In experiment 2, 250 pM siRNA for Cox-2 was introduced into CG cells for 0, 3, 6, 12, and 24 h. After culture, the amount of mRNA expression for Cox-2 was measured and the culture medium was collected to determine PGF2� concentration by enzyme immunoassay. The Cox-2 mRNA expression was not affected by 100 pM siRNA introduced into CG cells for 24 h, but 250 and 500 pM Cox-2 siRNA significantly reduced the Cox-2 mRNA expression (10% of that of the 0 pM siRNA group). Moreover, the suppressive effect of 250 pM siRNA was observed at 6 h after introduction (60% of that of the 0 pM siRNA group at 0 h) and the reduction of mRNA expression by RNAi became more obvious over 12 h (10% of that of the 0 pM siRNA group at 0 h). On the other hand, the PGF2� concentration in the culture medium was not significantly different at 12 h after siRNA introduction, however, the PGF2� concentration of the RNAi treatment group at 24 h was significantly lower than that of the 0 pM siRNA group at the same time point. These results suggest that gene silencing by Cox-2 siRNA is a means of analyzing the function and expression of specific genes in bovine CG cells. This study was supported by the Japan Society for the Promotion of Science for Young Scientists.

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