title: 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-κB (NF-κB)-dependent transcription of the EP3 gene by the activation of peroxisome proliferator-activated receptor-γ (PPAR-γ). Finally, chromatin immunoprecipitation revealed decreased binding of NF-κB to the EP3 promoter with oxLDL and PPAR-γ agonist treatment. Our results show that oxLDL suppresses EP3 expression by activation of PPAR-γ and subsequent inhibition of NF-κB 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.
authors.affiliation: Department of Cell Biology, Key Laboratory of Molecular Biology in High Cancer Incidence Coastal Chaoshan Area of Guangdong Higher Education Institutes, Shantou University Medical College, Shantou, Guangdong, China.
authors.forename: Xuxia
authors.initials: X
authors.lastname: Sui
authors.affiliation: Department of Cell Biology, Key Laboratory of Molecular Biology in High Cancer Incidence Coastal Chaoshan Area of Guangdong Higher Education Institutes, Shantou University Medical College, Shantou, Guangdong, China.
authors.forename: Yanmin
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Cell Biology, Key Laboratory of Molecular Biology in High Cancer Incidence Coastal Chaoshan Area of Guangdong Higher Education Institutes, Shantou University Medical College, Shantou, Guangdong, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Cell Biology, Key Laboratory of Molecular Biology in High Cancer Incidence Coastal Chaoshan Area of Guangdong Higher Education Institutes, Shantou University Medical College, Shantou, Guangdong, China.
authors.forename: Gefei
authors.initials: G
authors.lastname: Liu
authors.affiliation: Department of Cell Biology, Key Laboratory of Molecular Biology in High Cancer Incidence Coastal Chaoshan Area of Guangdong Higher Education Institutes, Shantou University Medical College, Shantou, Guangdong, China.
authors.forename: Xuhong
authors.initials: X
authors.lastname: Song
authors.affiliation: Department of Cell Biology, Key Laboratory of Molecular Biology in High Cancer Incidence Coastal Chaoshan Area of Guangdong Higher Education Institutes, Shantou University Medical College, Shantou, Guangdong, China.
authors.forename: Zhongjing
authors.initials: Z
authors.lastname: Su
authors.affiliation: Department of Cell Biology, Key Laboratory of Molecular Biology in High Cancer Incidence Coastal Chaoshan Area of Guangdong Higher Education Institutes, Shantou University Medical College, Shantou, Guangdong, China.
authors.forename: Xiaolan
authors.initials: X
authors.lastname: Chang
authors.affiliation: Department of Cardiovascular Research Center, Shantou University Medical College, Shantou, Guangdong, China.
authors.forename: Yingbi
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Cell Biology, Key Laboratory of Molecular Biology in High Cancer Incidence Coastal Chaoshan Area of Guangdong Higher Education Institutes, Shantou University Medical College, Shantou, Guangdong, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Liang
authors.affiliation: Department of Cell Biology, Key Laboratory of Molecular Biology in High Cancer Incidence Coastal Chaoshan Area of Guangdong Higher Education Institutes, Shantou University Medical College, Shantou, Guangdong, China.
authors.forename: Dongyang
authors.initials: D
authors.lastname: Huang
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008077:Lipoproteins, LDL / Q000008:administration & dosage* / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000096:biosynthesis; D047495:PPAR gamma / Q000096:biosynthesis* / Q000235:genetics; D058226:Plaque, Atherosclerotic / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis; D058308:Receptors, Prostaglandin E, EP3 Subtype / Q000096:biosynthesis* / Q000235:genetics; D013755:Tetradecanoylphorbol Acetate / Q000008:administration & dosage / Q000031:analogs & derivatives
chemical_list: D008077:Lipoproteins, LDL; D016328:NF-kappa B; D047495:PPAR gamma; C545647:PTGER3 protein, human; D012333:RNA, Messenger; D058308:Receptors, Prostaglandin E, EP3 Subtype; C099252:oxidized low density lipoprotein; C020922:4-O-methyl-12-O-tetradecanoylphorbol 13-acetate; D013755:Tetradecanoylphorbol Acetate