Overexpression of COX-2, Prostaglandin E Synthase-1 and Prostaglandin E Receptors in blood mononuclear cells and plaque of patients with carotid atherosclerosis: Regulation by nuclear factor-κB

Gómez-Hernández, Almudena; Martı́n-Ventura, José Luis; Sánchez-Galán, Eva; Vidal, Cristina; Ortego, Mónica; Blanco-Colio, Luís Miguel; Ortega, Luís; Tuñón, José; Egido, Jesús

doi:10.1016/j.atherosclerosis.2005.08.035

Cited by 85 publications

(79 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In the present study, we observed that the protein level of Cox-2 was significantly reduced in VSMCs treated with parthenolide for 2~12 h compared with cells cultured with 10% FBS alone (Fig.4). Recent studies have reported inhibitory effect of parthenolide on Cox-2 expression in monocytic cells and lipopolysaccharide-stimulated macrophages and in cancers (Gomez-Hernandez et al, 2006;Smolinski and Pestka, 2005). Since the expression of Cox-2 has been shown to be regulated by NF-κB (Dubois et al, 1998;Moon et al, 2004), our results may suggest that parthenolide upregulates the expression of IκBα protein and subsequently inhibits NF-κB activity, thus reducing the expression of Cox-2 protein.…”

Section: Discussionsupporting

confidence: 51%

Parthenolide inhibits proliferation of vascular smooth muscle cells through induction of G0/G1 phase cell cycle arrest

Weng

Sui

Chen

et al. 2009

J. Zhejiang Univ. Sci. B

View full text Add to dashboard Cite

Abstract:Objective: This study is to determine the effect of the natural product parthenolide, a sesquiterpene lactone isolated from extracts of the herb Tanacetum parthenium, on the proliferation of vascular smooth muscle cells (VSMCs). Methods: Rat aortic VSMCs were isolated and cultured in vitro, and treated with different concentrations of parthenolide (10, 20 and 30 μmol/L).[ 3 H]thymidine incorporation was used as an index of cell proliferation. Cell cycle progression and distribution were determined by flow cytometric analysis. Furthermore, the expression of several regulatory proteins relevant to VSMC proliferation including IκBα, cyclooxygenase-2 (Cox-2), p21, and p27 was examined to investigate the potential molecular mechanism. Results: Treatment with parthenolide significantly decreased the [ 3 H]thymidine incorporation into DNA by 30%~56% relative to control values in a dose-dependent manner (P<0.05). Addition of parthenolide also increased cell population at G 0 /G 1 phase by 19.2%~65.7% (P<0.05) and decreased cell population at S phase by 50.7%~84.8% (P<0.05), which is consistent with its stimulatory effects on p21 and p27. In addition, parthenolide also increased IκBα expression and reduced Cox-2 expression in a time-dependent manner. Conclusion: Our results show that parthenolide significantly inhibits the VSMC proliferation by inducing G 0 /G 1 cell cycle arrest. IκBα and Cox-2 are likely involved in such inhibitory effect of parthenolide on VSMC proliferation. These findings warrant further investigation on potential therapeutic implications of parthenolide on VSMC proliferation in vivo.

show abstract

Section: Discussionsupporting

confidence: 51%

Parthenolide inhibits proliferation of vascular smooth muscle cells through induction of G0/G1 phase cell cycle arrest

Weng

Sui

Chen

et al. 2009

J. Zhejiang Univ. Sci. B

View full text Add to dashboard Cite

show abstract

“…Significance of mPGES-1 Inhibition-PGE 2 is a key proinflammatory mediator of inflammation associated with various disease states, and increased PGE 2 requires both COX-2 and mPGES-1 (4,5,18,19,(35)(36)(37)(38). Nonselective and COX-2-selective NSAIDs reduce PGE 2 production by inhibiting COX-2 activity and are extensively used for reducing inflammation, pain, and fever (39).…”

Section: Discussionmentioning

confidence: 99%

Microsomal Prostaglandin E Synthase-1 Deficiency Is Associated with Elevated Peroxisome Proliferator-activated Receptor γ

Kapoor

Kojima

Qian

et al. 2007

Journal of Biological Chemistry

View full text Add to dashboard Cite

mPGES-1 (microsomal PGE synthase-1) is an inducible enzyme that acts downstream of cyclooxygenase (COX) and specifically catalyzes the conversion of prostaglandin (PG) H 2 to PGE 2 under basal as well as inflammatory conditions. In this study, using mouse embryo fibroblasts (MEFs) isolated from mice genetically deficient for the mPges-1 gene, we show basal elevation of peroxisome proliferator-activated receptor ␥ (PPAR␥) expression (protein and mRNA) and transcriptional activity associated with reduced basal PGE 2 . We further show that basal mPGES-1-derived PGE 2 suppresses the expression of PPAR␥ through a cAMP-independent pathway involving phosphatidylinositol 3-kinase and Akt signaling. Using specific PPAR␥ agonist (rosiglitazone), PPAR␥ ligand (15-deoxy-⌬12,14-PGJ 2 ), and PPAR␥ inhibitor (GW9662), we confirm that activation of PPAR␥ blocks interleukin-1␤-induced up-regulation of COX-2, mPGES-1, and their derived PGE 2 . Furthermore, we demonstrate that up-regulation of PPAR␥ upon genetic deletion of mPGES-1 is responsible for reduced COX-2 expression under basal as well as interleukin-1␤-stimulated conditions. This study provides evidence for the first time that mPGES-1 deletion not only decreases proinflammatory PGE 2 but also up-regulates anti-inflammatory PPAR␥, which has the ability to suppress COX-2 and mPGES-1 expression and PGE 2 production. Thus, mPGES-1 inhibition may limit inflammation by multiple mechanisms and is a potential therapeutic target. Prostaglandins (PGs)2 are formed by metabolism of arachidonic acid by cyclooxygenases (COX) to generate an intermediate substrate, PGH 2 , which is further metabolized by terminal synthases to generate specific PGs (1, 2). mPGES-1, originally known as microsomal glutathione S-transferase 1-like 1 (MGST1-L1), is an inducible enzyme that acts downstream of COX and specifically catalyzes the conversion of PGH 2 to PGE 2 (3), most prominently in inflammatory conditions (4, 5). However, we have recently shown that mPGES-1 is critical for PGE 2 production under basal as well as inflammatory conditions (6).mPGES-1 is coordinately induced with COX-2 by inflammatory stimuli in a variety of cells and tissues (4, 7). PGE 2 is the most abundant PG associated with inflammatory conditions, and overproduction of PGE 2 coincides with increased COX-2 and mPGES-1 expression (4, 7). PGE 2 exerts the majority of its actions through a family of G protein-coupled receptors, including EP1, EP2, EP3, and EP4 (8). The effects of PGE 2 via these receptors are mediated through various downstream signaling pathways, including cAMP-dependent protein kinase, mitogen-activated protein kinase (MAP kinase), phosphatidylinositol 3-kinase (PI 3-kinase), and Akt (8 -10).Inhibition of PGE 2 production and action is associated with reduction of the pain and inflammation associated with a wide variety of diseases. Nonselective and COX-2-selective nonsteroidal anti-inflammatory drugs (NSAIDs) block PGE 2 production by inhibiting the activity of COX and are extensively used to treat arthritis a...

show abstract

“…Eventually, cytokine levels may attain sufficient levels to promote systemic effects, and several plasma inflammatory biomarkers are measurable and the plasma concentrations may parallel the course of CHD. Potential biomarkers include plasminogen activator inhibitor-I [17], prostaglandin E1 and E2 [18] and C-reactive protein [19]. Concomitant with changes in cytokine levels, plasma lipid profiles are converted to a more atherogenic profile with high lowdensity lipoprotein (LDL) and triglycerides, high total and free cholesterol and low HDLc.…”

Section: Introductionmentioning

confidence: 99%

Regulation of high‐density lipoprotein by inflammatory cytokines: establishing links between immune dysfunction and cardiovascular disease

Haas

Mooradian

2010

Diabetes Metabolism Res

View full text Add to dashboard Cite

Coronary artery disease is a primary co-morbidity in metabolic diseases such as metabolic syndrome, diabetes and obesity. One contributing risk factor for coronary artery disease is low high-density lipoprotein-cholesterol (HDLc). Several factors influence steady-state HDLc levels, including diet, genetics and environment. Perhaps more important to coronary artery disease is factors that attribute to the dynamics of reverse cholesterol transport, storage, and excretion of excess cholesterol. HDLc biogenesis, clearance and innate ability to serve as a cholesterol acceptor and transporter all contribute to HDLc's function as a negative regulator of cardiovascular disease. With the recent failure of torcetrapid, focus is being placed on HDLc biology and its role in various metabolic diseases. Low HDLc levels are often associated with an increased state of background inflammation. Recently, several syndromes with clear pro-inflammatory components have been shown to be inversely correlated with low HDLc levels in the absence of obesity, diabetes and metabolic syndrome. Early studies with HDLc during the acute-phase response suggest that HDLc is substantially physically modified during acute infection and sepsis, and recent studies show that HDLc is physically modified by chronic pro-inflammatory disease. In this review, several of these connections are described and cytokine signalling related to HDLc is examined.

show abstract

Overexpression of COX-2, Prostaglandin E Synthase-1 and Prostaglandin E Receptors in blood mononuclear cells and plaque of patients with carotid atherosclerosis: Regulation by nuclear factor-κB

Cited by 85 publications

References 40 publications

Parthenolide inhibits proliferation of vascular smooth muscle cells through induction of G0/G1 phase cell cycle arrest

Parthenolide inhibits proliferation of vascular smooth muscle cells through induction of G0/G1 phase cell cycle arrest

Microsomal Prostaglandin E Synthase-1 Deficiency Is Associated with Elevated Peroxisome Proliferator-activated Receptor γ

Regulation of high‐density lipoprotein by inflammatory cytokines: establishing links between immune dysfunction and cardiovascular disease

Contact Info

Product

Resources

About