Human Vascular Smooth Muscle Cells but Not Endothelial Cells Express Prostaglandin E Synthase

Soler, Marta; Camacho, Mercedes; Escudero, José Román; Íñiguez, Miguel A.; Vilá, Luis M.

doi:10.1161/01.res.87.6.504

Cited by 105 publications

(84 citation statements)

References 31 publications

(24 reference statements)

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“…60 Similar to the present results, the expression of PGE synthases and the up-regulation of mPGES-1, COX-2, and PGE 2 in response to IL-1␤ and TNF-␣ have also been demonstrated in primary human vascular smooth muscle cells. 61,62 In one of those studies, 62 the authors also demonstrated the lack of mPGES-1 induction in HUVEC cells, which is in accord with our results obtained from HUVEC cells. The substantial increase in expression of PGE synthases and subsequently increased PGE 2 pro- duction observed in smooth muscle cells in the present study highlights these cells as potentially an important cell type contributing to the elevated levels of PGE 2 in gingival tissue.…”

Section: Discussionsupporting

confidence: 90%

Expression of Prostaglandin E Synthases in Periodontitis

Båge

Kats

Lopez

et al. 2011

The American Journal of Pathology

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The inflammatory mediator prostaglandin E 2 (PGE 2 ) is implicated in the pathogenesis of chronic inflammatory diseases including periodontitis; it is synthesized by cyclooxygenases (COX) and the prostaglandin E synthases mPGES-1, mPGES-2, and cPGES. The distribution of PGES in gingival tissue of patients with periodontitis and the contribution of these enzymes to inflammationinduced PGE 2 synthesis in different cell types was investigated. In gingival biopsies, positive staining for PGES was observed in fibroblasts and endothelial, smooth muscle, epithelial, and immune cells. To further explore the contribution of PGES to inflammation-induced PGE 2 production, in vitro cell culture experiments were performed using fibroblasts and endothelial, smooth muscle, and mast cells. All cell types expressed PGES and COX-2, resulting in basal levels of PGE 2 synthesis. In response to tumor necrosis factor (TNF-␣), IL-1␤, and cocultured lymphocytes, however, mPGES-1 and COX-2 protein expression increased in fibroblasts and smooth muscle cells, accompanied by increased PGE 2 , whereas mPGES-2 and cPGES were unaffected. In endothelial cells, TNF-␣ increased PGE 2 production only via COX-2 expression, whereas in mast cells the cytokines did not affect PGE 2 enzyme expression or PGE 2 production. Furthermore, PGE 2 production was diminished in gingival fibroblasts derived from mPGES-1 knockout mice, compared with wild-type fibroblasts. These results suggest that fibroblasts and smooth muscle cells are important sources of mPGES-1, which may contribute to increased PGE 2 production in the inflammatory condition periodontitis.

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Section: Discussionsupporting

confidence: 90%

Expression of Prostaglandin E Synthases in Periodontitis

Båge

Kats

Lopez

et al. 2011

The American Journal of Pathology

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“…This is supported by recent evidence suggesting co-ordinate up-and down-regulation of mPGES and COX-2 ( Thoren and Jakobsson, 2000). Previous studies have detected expression of mPGES in human smooth muscle vascular cells but not in umbilical vein endothelial cells although these cells retained synthetic capacity for PGE 2 (Soler et al, 2000). This apparent discrepancy may reflect tissue variation in regulation of expression of mPGES in endothelial cells.…”

Section: Cox-2 and Pge 2 In Endometrial Adenocarcinoma 1027supporting

confidence: 66%

Expression of COX-2 and PGE synthase and synthesis of PGE2in endometrial adenocarcinoma: a possible autocrine/paracrine regulation of neoplastic cell function via EP2/EP4 receptors

et al. 2001

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Summary This study was designed to investigate the possible role of cyclo-oxygenase-2 (COX-2) and prostaglandin E 2 (PGE 2 ) in endometrial adenocarcinoma. COX-2 RNA expression was confirmed in various grades of adenocarcinoma by ribonuclease protection assay. COX-2 and microsomal glutathione-dependent prostaglandin E synthase (mPGES) expression and PGE 2 synthesis were localised to the neoplastic epithelial cells and endothelial cells. In order to establish whether PGE 2 has an autocrine/paracrine effect in adenocarcinomas, we investigated the expression of 2 subtypes of PGE 2 receptors, namely EP2 and EP4, by real time quantitative PCR. Expression of EP2 and EP4 receptors was detected in adenocarcinomas from all grades of differentiation and was significantly higher than that detected in normal secretory phase endometrium (P < 0.01). The fold induction of expression in adenocarcinoma compared with normal secretory phase endometrium was 28.0 ± 7.4 and 52.5 ± 10.1 for EP2 and EP4 receptors respectively. Immunohistochemistry localised the site of expression of EP4 receptor in neoplastic epithelial cells and in the endothelium of carcinomas of all grades of differentiation. Finally, the functionality of the EP2/EP4 receptors was assessed by investigating cAMP generation following in vitro culture of adenocarcinoma tissue in the presence or absence of 300 nM PGE 2 . cAMP production in response to PGE 2 was significantly higher in carcinoma tissue than that detected in normal secretory phase endometrium (3.42 ± 0.46 vs 1.15 ± 0.05 respectively; P < 0.001). In conclusion, these data suggest that PGE 2 may regulate neoplastic cell function in an autocrine/paracrine manner via the EP2/EP4 receptors.

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“…In contrast, expression of COX-2 generally requires exposure to pro-inflammatory stimuli such as TNF-␣, IL-1␤, IFN-␥, CD40 ligand, or LPS (9, 39, 40). Among cells found in atheroma, SMC elaborate PGE 2 in response to pro-inflammatory stimuli, accompanied by the in- duction of COX-2 protein (13,18,41). Using M⌽ co-cultured with SMC, we demonstrated that SMC-derived PGE 2 can reduce MIP-1␤ production in M⌽.…”

Section: Discussionmentioning

confidence: 85%

Prostaglandin E2 Suppresses Chemokine Production in Human Macrophages through the EP4 Receptor

Takayama¹,

García‐Cardeña

Sukhova³

et al. 2002

Journal of Biological Chemistry

306

272

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Pro-inflammatory pathways participate in the pathogenesis of atherosclerosis. However, the role of endogenous anti-inflammatory pathways in atheroma has received much less attention. Therefore, using cDNA microarrays, we screened for genes regulated by prostaglandin E 2 (PGE 2 ), a potential endogenous anti-inflammatory mediator, in lipopolysaccharide (LPS)-treated human macrophages (M⌽). PGE 2 (50 nM) attenuated LPS-induced mRNA and protein expression of chemokines including monocyte chemoattractant protein-1, interleukin-8, macrophage inflammatory protein-1␣ and -1␤, and interferon-inducible protein-10. PGE 2 also inhibited the tumor necrosis factor-␣-, interferon-␥-, and interleukin-1␤-mediated expression of these chemokines. In contrast to the case of M⌽, PGE 2 did not suppress chemokine expression in human endothelial and smooth muscle cells (SMC) treated with LPS and pro-inflammatory cytokines. To assess the potential paracrine effect of endogenous PGE 2 on macrophagederived chemokine production, we co-cultured M⌽ with SMC in the presence of LPS. In these co-cultures, cyclooxygenase-2-dependent PGE 2 production exceeded that in the mono-cultures, and MIP-1␤ declined significantly compared with M⌽ cultured without SMC. We further documented prominent expression of the PGE 2 receptor EP4 in M⌽ in both culture and human atheroma. Moreover, a selective EP4 antagonist completely reversed PGE 2 -mediated suppression of chemokine production. Thus, endogenous PGE 2 may modulate inflammation during atherogenesis and other inflammatory diseases by suppressing macrophage-derived chemokine production via the EP4 receptor.

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Human Vascular Smooth Muscle Cells but Not Endothelial Cells Express Prostaglandin E Synthase

Cited by 105 publications

References 31 publications

Expression of Prostaglandin E Synthases in Periodontitis

Expression of Prostaglandin E Synthases in Periodontitis

Expression of COX-2 and PGE synthase and synthesis of PGE2in endometrial adenocarcinoma: a possible autocrine/paracrine regulation of neoplastic cell function via EP2/EP4 receptors

Prostaglandin E2 Suppresses Chemokine Production in Human Macrophages through the EP4 Receptor

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