Dataset Information

Oxidized low-density lipoprotein suppresses expression of prostaglandin E receptor subtype EP3 in human THP-1 macrophages.

ABSTRACT: EP3, one of four prostaglandin E2 (PGE2) receptors, is significantly lower in atherosclerotic plaques than in normal arteries and is localized predominantly in macrophages of the plaque shoulder region. However, mechanisms behind this EP3 expression pattern are still unknown. We investigated the underlying mechanism of EP3 expression in phorbol 12-myristate 13-acetate (PMA)-differentiated THP-1 macrophages with oxidized low-density lipoprotein (oxLDL) treatment. We found that oxLDL decreased EP3 expression, in a dose-dependent manner, at both the mRNA and protein levels. Moreover, oxLDL inhibited nuclear factor-?B (NF-?B)-dependent transcription of the EP3 gene by the activation of peroxisome proliferator-activated receptor-? (PPAR-?). Finally, chromatin immunoprecipitation revealed decreased binding of NF-?B to the EP3 promoter with oxLDL and PPAR-? agonist treatment. Our results show that oxLDL suppresses EP3 expression by activation of PPAR-? and subsequent inhibition of NF-?B in macrophages. These results suggest that down-regulation of EP3 expression by oxLDL is associated with impairment of EP3-mediated anti-inflammatory effects, and that EP3 receptor activity may exert a beneficial effect on atherosclerosis.

SUBMITTER: Sui X

PROVIDER: S-EPMC4205008 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Oxidized low-density lipoprotein suppresses expression of prostaglandin E receptor subtype EP3 in human THP-1 macrophages.

Sui Xuxia X Liu Yanmin Y Li Qi Q Liu Gefei G Song Xuhong X Su Zhongjing Z Chang Xiaolan X Zhou Yingbi Y Liang Bin B Huang Dongyang D

PloS one 20141021 10

EP3, one of four prostaglandin E2 (PGE2) receptors, is significantly lower in atherosclerotic plaques than in normal arteries and is localized predominantly in macrophages of the plaque shoulder region. However, mechanisms behind this EP3 expression pattern are still unknown. We investigated the underlying mechanism of EP3 expression in phorbol 12-myristate 13-acetate (PMA)-differentiated THP-1 macrophages with oxidized low-density lipoprotein (oxLDL) treatment. We found that oxLDL decreased EP3 ...[more]

PMID: 25333975

Similar Datasets

Project description:Introduction: Oxidative stress in monocyte-derived macrophages is a significant pathophysiological process in atherosclerosis. L-cystathionine (L-Cth) acts as a scavenger for oxygen free radicals. However, the impact of L-Cth on macrophage oxidative stress during atherogenesis has remained unclear. This study aimed to investigate whether L-Cth affects oxidative stress in THP-1-derived macrophages and its subsequent effects on DNA damage and cell apoptosis. Methods: We established a cellular model of oxLDL-stimulated macrophages. The content of superoxide anion, H2O2, NO, and H2S in the macrophage were in situ detected by the specific fluorescence probe, respectively. The activities of SOD, GSH-Px, and CAT were measured by colorimetrical assay. The protein expressions of SOD1, SOD2, and iNOS were detected using western blotting. The DNA damage and apoptosis in the macrophage was evaluated using an fluorescence kit. Results: The results demonstrated that oxLDL significantly increased the content of superoxide anion and H2O2, the expression of iNOS protein, and NO production in macrophages. Conversely, oxLDL decreased the activity of antioxidants GSH-Px, SOD, and CAT, and downregulated the protein expressions of SOD1 and SOD2 in macrophages. However, treatment with L-Cth reduced the levels of superoxide anion, H2O2, and NO, as well as the protein expression of iNOS induced by oxLDL. Moreover, L-Cth treatment significantly enhanced GSH-Px, SOD, and CAT activity, and upregulated the expressions of SOD1 and SOD2 proteins in macrophages treated with oxLDL. Furthermore, both L-Cth supplementation and activation of endogenous L-Cth production suppressed DNA damage and cell apoptosis in oxLDL-injured macrophages, whereas inhibition of endogenous L-Cth exacerbated the deleterious effects of oxLDL. Conclusion: These findings suggest that L-Cth exerts a pronounced inhibitory effect on the oxidative stress, subsequent DNA damage and cell apoptosis in oxLDL-stimulated THP-1 monocytes. This study deepens our understanding of the pathogenesis of macrophage-related cardiovascular pathology.

Dataset Information

Oxidized low-density lipoprotein suppresses expression of prostaglandin E receptor subtype EP3 in human THP-1 macrophages.

Publications

Oxidized low-density lipoprotein suppresses expression of prostaglandin E receptor subtype EP3 in human THP-1 macrophages.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets