title: C1q/TNF-related protein-9 inhibits cytokine-induced vascular inflammation and leukocyte adhesiveness via AMP-activated protein kinase activation in endothelial cells.
abstract: Although recent studies have reported cardioprotective effects of C1q/TNF-related protein 9 (CTRP9), the closet adiponectin paralog, its role on cytokine-induced endothelial inflammation is unknown. We investigated whether CTRP9 prevented inflammatory cytokine-induced nuclear factor-kappa B (NF-κB) activation and inhibited the expression of adhesion molecules and a chemokine in the vascular endothelial cell. We used human aortic endothelial cells (HAECs) to examine the effects of CTRP9 on NF-κB activation and the expression of NF-κB-mediated genes, including intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and monocyte chemoattractant protein-1 (MCP-1). Tumor necrosis factor alpha (TNFα) was used as a representative proinflammatory cytokine. In an adhesion assay using THP-1 cells, CTRP9 reduced TNFα-induced adhesion of monocytes to HAECs. Treatment with CTRP9 significantly decreased TNFα-induced activation of NF-κB, as well as the expression of ICAM-1, VCAM-1, and MCP-1. In addition, treatment with CTRP9 significantly increased the phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC), the downstream target of AMPK. The inhibitory effect of CTRP9 on the expression of ICAM-1, VCAM-1, and MCP-1 and monocyte adhesion to HAECs was abolished after transfection with an AMPKα1-specific siRNA. Our study is the first to demonstrate that CTRP9 attenuates cytokine-induced vascular inflammation in endothelial cells mediated by AMPK activation.
authors.affiliation: Department of Internal Medicine, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Chang Hee
authors.initials: CH
authors.lastname: Jung
authors.affiliation: Department of Internal Medicine, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Min Jung
authors.initials: MJ
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Yu Mi
authors.initials: YM
authors.lastname: Kang
authors.affiliation: Asan Institute of Life Sciences, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Yoo La
authors.initials: YL
authors.lastname: Lee
authors.affiliation: Asan Institute of Life Sciences, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: So Mi
authors.initials: SM
authors.lastname: Seol
authors.affiliation: Asan Institute of Life Sciences, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Hae Kyeong
authors.initials: HK
authors.lastname: Yoon
authors.affiliation: Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Sang-Wook
authors.initials: SW
authors.lastname: Kang
authors.affiliation: Department of Internal Medicine, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Woo Je
authors.initials: WJ
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, University of Ulsan College of Medicine, Seoul, Republic of Korea. Electronic address: jypark@amc.seoul.kr.
authors.forename: Joong-Yeol
authors.initials: JY
authors.lastname: Park
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D052242:Adiponectin / Q000494:pharmacology*; D001011:Aorta / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D045744:Cell Line, Tumor; D018932:Chemokine CCL2 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006023:Glycoproteins / Q000494:pharmacology*; D006801:Humans; D016328:NF-kappa B / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D015398:Signal Transduction; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D052242:Adiponectin; C543615:C1QTNF9B protein, human; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D016207:Cytokines; D006023:Glycoproteins; D016328:NF-kappa B; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins; D019010:Vascular Cell Adhesion Molecule-1; D055372:AMP-Activated Protein Kinases
keywords: AMPK; Adhesion molecules; CTRP9; Endothelial cells; NF-κB