title: LECT2 induces atherosclerotic inflammatory reaction via CD209 receptor-mediated JNK phosphorylation in human endothelial cells.
abstract: OBJECTIVE
  Leukocyte cell-derived chemotaxin 2 (LECT2) is a recently discovered novel hepatokine, leading to skeletal muscle insulin resistance by activating c-Jun N-terminal kinase (JNK). However, its role in atherosclerotic inflammatory reactions has not been examined. Therefore, we investigated the function of LECT2 on the expression of vascular adhesion molecules and inflammatory cytokines in human endothelial cells.
  
  
  METHODS
  Human umbilical vein endothelial cells (HUVECs) and THP-1 cells were treated with various doses of LECT2 and the functions and signaling pathways were analyzed through Western blot and quantitative real-time PCR (qPCR).
  
  
  RESULTS
  The level of phosphorylated c-Jun N-terminal kinases (JNK) was significantly increased by LECT2 treatment in HUVECs and THP-1 cells, an effect that was not seen in cells treated with CD209 siRNA, a known LECT2 receptor. LECT2 treatment efficiently increased the expression of intercellular adhesion molecule-1 (ICAM-1) and pro-inflammatory cytokines tumor necrosis factor α (TNFα), monocyte chemo-attractant protein-1 (MCP-1), and interleukin-1β (IL-1β) in HUVECs and THP-1 cells. However, all these reactions were significantly reduced in response to treatment with JNK inhibitor. Furthermore, LECT2 treatment significantly exacerbated the adhesion of monocytic cells to human endothelial cells, which was also efficiently attenuated by JNK inhibitor.
  
  
  CONCLUSIONS
  LECT2 significantly induced adhesion molecules and pro-inflammatory cytokines in HUVECs via CD209-mediated JNK phosphorylation, suggesting that liver-derived novel hepatokine, LECT2, might directly mediate in the atherosclerotic inflammatory reactions in human endothelial cells.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Korea University, Seoul, Korea.
authors.forename: Hwan-Jin
authors.initials: HJ
authors.lastname: Hwang
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Korea University, Seoul, Korea.
authors.forename: Tae Woo
authors.initials: TW
authors.lastname: Jung
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Korea University, Seoul, Korea.
authors.forename: Ho Cheol
authors.initials: HC
authors.lastname: Hong
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Korea University, Seoul, Korea.
authors.forename: Ji A
authors.initials: JA
authors.lastname: Seo
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Korea University, Seoul, Korea.
authors.forename: Sin Gon
authors.initials: SG
authors.lastname: Kim
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Korea University, Seoul, Korea.
authors.forename: Nan Hee
authors.initials: NH
authors.lastname: Kim
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Korea University, Seoul, Korea.
authors.forename: Kyung Mook
authors.initials: KM
authors.lastname: Choi
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Korea University, Seoul, Korea.
authors.forename: Dong Seop
authors.initials: DS
authors.lastname: Choi
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Korea University, Seoul, Korea.
authors.forename: Sei Hyun
authors.initials: SH
authors.lastname: Baik
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Korea University, Seoul, Korea. Electronic address: deisy21@naver.com.
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: Yoo
mesh_terms: D050197:Atherosclerosis / Q000139:chemically induced* / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D016207:Cytokines / Q000096:biosynthesis; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007249:Inflammation / Q000139:chemically induced* / Q000473:pathology; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology*; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D037181:Lectins, C-Type / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D015815:Cell Adhesion Molecules; D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins; D048031:JNK Mitogen-Activated Protein Kinases; D037181:Lectins, C-Type; D047428:Protein Kinase Inhibitors; D034741:RNA, Small Interfering; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C103468:LECT2 protein, human
keywords: Atherosclerosis; Inflammation; Leukocyte cell-derived chemotaxin 2; c-Jun N-terminal kinases