title: Angiotensin II-induced Egr-1 expression is suppressed by peroxisome proliferator-activated receptor-γ ligand 15d-PGJ₂ in macrophages.
abstract: OBJECTIVE
  Angiotensin II (Ang II) plays a critical role in regulating vascular inflammatory diseases, such as atherosclerosis and hypertension. Early growth response-1 (Egr-1) is an immediate early gene that acts as a master switch for the inflammatory response. However, the role of Ang II in regulating Egr-1 expression in macrophages, and the effect of peroxisome proliferators-activated receptor-γ (PPAR-γ) ligand 15d-PGJ2 in this process remain to be investigated.
  
  
  RESULTS
  We showed that Ang II significantly up-regulated the expression of Egr-1 in RAW264.7 macrophages, and this effect was markedly attenuated by Eprosartan (an AT1R blocker), SP600125 (a JNK-specific inhibitor) and PD98059 (an ERK-specific inhibitor). Moreover, treatment of macrophages with 15d-PGJ2, a natural PPAR-γ ligand, significantly reduced Ang II-induced expression of Egr-1 and its inflammatory gene targets (IL-1β, TNF-α, TGF-β, MCP-1 and ICAM-1) through PPAR-γ activation and ROS formation. In addition, 15d-PGJ2 treatment markedly inhibited Ang II-induced macrophage migration and proliferation.
  
  
  CONCLUSIONS
  This study for the first time demonstrates that Ang II can induce the expression of Egr-1 via AT1R/JNK and ERK signaling pathways. Activation of PPAR-γ by 15d-PGJ2 suppresses Egr-1-mediated proinflammatory response, and may be a novel therapeutic strategy for treatment of vascular inflammatory diseases.
authors.affiliation: Department of Pathology and Pathophysiology, School of Basic Medical Sciences, Beijing AnZhen Hospital, the Key Laboratory of Remodeling-related Cardiovascular Diseases, Capital Medical University, Ministry of Education, Beijing, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Meng
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
authors.forename: Cui
authors.initials: C
authors.lastname: Tian
authors.forename: Jie
authors.initials: J
authors.lastname: Du
authors.forename: Hui-Hua
authors.initials: HH
authors.lastname: Li
mesh_terms: D000179:Acrylates / Q000494:pharmacology; D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism*; D051766:Early Growth Response Protein 1 / Q000378:metabolism*; D005419:Flavonoids / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000494:pharmacology; D013876:Thiophenes / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects
chemical_list: C477819:15-deoxyprostaglandin J2; D000179:Acrylates; D000873:Anthracenes; D016207:Cytokines; D051766:Early Growth Response Protein 1; C486109:Egr1 protein, mouse; D005419:Flavonoids; D007093:Imidazoles; D013876:Thiophenes; D000804:Angiotensin II; C432165:pyrazolanthrone; C068373:eprosartan; D015230:Prostaglandin D2; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one