PMID- 26523509 OWN - NLM STAT- MEDLINE DCOM- 20161006 LR - 20191210 IS - 1872-8057 (Electronic) IS - 0303-7207 (Linking) VI - 419 DP - 2016 Jan 5 TI - C1q/TNF-related protein-9 inhibits cytokine-induced vascular inflammation and leukocyte adhesiveness via AMP-activated protein kinase activation in endothelial cells. PG - 235-43 LID - S0303-7207(15)30123-4 [pii] LID - 10.1016/j.mce.2015.10.023 [doi] AB - 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-kappaB) 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-kappaB activation and the expression of NF-kappaB-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 (TNFalpha) was used as a representative proinflammatory cytokine. In an adhesion assay using THP-1 cells, CTRP9 reduced TNFalpha-induced adhesion of monocytes to HAECs. Treatment with CTRP9 significantly decreased TNFalpha-induced activation of NF-kappaB, 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 AMPKalpha1-specific siRNA. Our study is the first to demonstrate that CTRP9 attenuates cytokine-induced vascular inflammation in endothelial cells mediated by AMPK activation. CI - Copyright (c) 2015 Elsevier Ireland Ltd. All rights reserved. FAU - Jung, Chang Hee AU - Jung CH AD - Department of Internal Medicine, University of Ulsan College of Medicine, Seoul, Republic of Korea. FAU - Lee, Min Jung AU - Lee MJ AD - Department of Internal Medicine, University of Ulsan College of Medicine, Seoul, Republic of Korea. FAU - Kang, Yu Mi AU - Kang YM AD - Department of Internal Medicine, University of Ulsan College of Medicine, Seoul, Republic of Korea. FAU - Lee, Yoo La AU - Lee YL AD - Asan Institute of Life Sciences, University of Ulsan College of Medicine, Seoul, Republic of Korea. FAU - Seol, So Mi AU - Seol SM AD - Asan Institute of Life Sciences, University of Ulsan College of Medicine, Seoul, Republic of Korea. FAU - Yoon, Hae Kyeong AU - Yoon HK AD - Asan Institute of Life Sciences, University of Ulsan College of Medicine, Seoul, Republic of Korea. FAU - Kang, Sang-Wook AU - Kang SW AD - Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul, Republic of Korea. FAU - Lee, Woo Je AU - Lee WJ AD - Department of Internal Medicine, University of Ulsan College of Medicine, Seoul, Republic of Korea. FAU - Park, Joong-Yeol AU - Park JY AD - Department of Internal Medicine, University of Ulsan College of Medicine, Seoul, Republic of Korea. Electronic address: jypark@amc.seoul.kr. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20151031 PL - Ireland TA - Mol Cell Endocrinol JT - Molecular and cellular endocrinology JID - 7500844 RN - 0 (Adiponectin) RN - 0 (C1QTNF9B protein, human) RN - 0 (CCL2 protein, human) RN - 0 (Chemokine CCL2) RN - 0 (Cytokines) RN - 0 (Glycoproteins) RN - 0 (NF-kappa B) RN - 0 (Tumor Necrosis Factor Receptor-Associated Peptides and Proteins) RN - 0 (Vascular Cell Adhesion Molecule-1) RN - EC 2.7.11.31 (AMP-Activated Protein Kinases) SB - IM MH - AMP-Activated Protein Kinases/*metabolism MH - Adiponectin/*pharmacology MH - Aorta/cytology/drug effects/metabolism MH - Cell Line, Tumor MH - Chemokine CCL2/metabolism MH - Cytokines/*metabolism MH - Endothelial Cells/cytology/*drug effects/metabolism MH - Gene Expression Regulation/drug effects MH - Glycoproteins/*pharmacology MH - Humans MH - NF-kappa B/*pharmacology MH - Phosphorylation/drug effects MH - Signal Transduction MH - Tumor Necrosis Factor Receptor-Associated Peptides and Proteins MH - Vascular Cell Adhesion Molecule-1/metabolism OTO - NOTNLM OT - AMPK OT - Adhesion molecules OT - CTRP9 OT - Endothelial cells OT - NF-kappaB EDAT- 2015/11/03 06:00 MHDA- 2016/10/08 06:00 CRDT- 2015/11/03 06:00 PHST- 2015/06/24 00:00 [received] PHST- 2015/10/02 00:00 [revised] PHST- 2015/10/25 00:00 [accepted] PHST- 2015/11/03 06:00 [entrez] PHST- 2015/11/03 06:00 [pubmed] PHST- 2016/10/08 06:00 [medline] AID - S0303-7207(15)30123-4 [pii] AID - 10.1016/j.mce.2015.10.023 [doi] PST - ppublish SO - Mol Cell Endocrinol. 2016 Jan 5;419:235-43. doi: 10.1016/j.mce.2015.10.023. Epub 2015 Oct 31.