PMID- 26123523
OWN - NLM
STAT- MEDLINE
DCOM- 20151109
LR  - 20150821
IS  - 1532-8600 (Electronic)
IS  - 0026-0495 (Linking)
VI  - 64
IP  - 9
DP  - 2015 Sep
TI  - LECT2 induces atherosclerotic inflammatory reaction via CD209 receptor-mediated 
      JNK phosphorylation in human endothelial cells.
PG  - 1175-82
LID - S0026-0495(15)00162-6 [pii]
LID - 10.1016/j.metabol.2015.06.001 [doi]
AB  - 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 
      alpha (TNFalpha), monocyte chemo-attractant protein-1 (MCP-1), and interleukin-1beta (IL-1beta) 
      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.
CI  - Copyright (c) 2015 Elsevier Inc. All rights reserved.
FAU - Hwang, Hwan-Jin
AU  - Hwang HJ
AD  - Division of Endocrinology and Metabolism, Department of Internal Medicine, 
      College of Medicine, Korea University, Seoul, Korea.
FAU - Jung, Tae Woo
AU  - Jung TW
AD  - Division of Endocrinology and Metabolism, Department of Internal Medicine, 
      College of Medicine, Korea University, Seoul, Korea.
FAU - Hong, Ho Cheol
AU  - Hong HC
AD  - Division of Endocrinology and Metabolism, Department of Internal Medicine, 
      College of Medicine, Korea University, Seoul, Korea.
FAU - Seo, Ji A
AU  - Seo JA
AD  - Division of Endocrinology and Metabolism, Department of Internal Medicine, 
      College of Medicine, Korea University, Seoul, Korea.
FAU - Kim, Sin Gon
AU  - Kim SG
AD  - Division of Endocrinology and Metabolism, Department of Internal Medicine, 
      College of Medicine, Korea University, Seoul, Korea.
FAU - Kim, Nan Hee
AU  - Kim NH
AD  - Division of Endocrinology and Metabolism, Department of Internal Medicine, 
      College of Medicine, Korea University, Seoul, Korea.
FAU - Choi, Kyung Mook
AU  - Choi KM
AD  - Division of Endocrinology and Metabolism, Department of Internal Medicine, 
      College of Medicine, Korea University, Seoul, Korea.
FAU - Choi, Dong Seop
AU  - Choi DS
AD  - Division of Endocrinology and Metabolism, Department of Internal Medicine, 
      College of Medicine, Korea University, Seoul, Korea.
FAU - Baik, Sei Hyun
AU  - Baik SH
AD  - Division of Endocrinology and Metabolism, Department of Internal Medicine, 
      College of Medicine, Korea University, Seoul, Korea.
FAU - Yoo, Hye Jin
AU  - Yoo HJ
AD  - Division of Endocrinology and Metabolism, Department of Internal Medicine, 
      College of Medicine, Korea University, Seoul, Korea. Electronic address: 
      deisy21@naver.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150606
PL  - United States
TA  - Metabolism
JT  - Metabolism: clinical and experimental
JID - 0375267
RN  - 0 (Cell Adhesion Molecules)
RN  - 0 (Cytokines)
RN  - 0 (DC-specific ICAM-3 grabbing nonintegrin)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (LECT2 protein, human)
RN  - 0 (Lectins, C-Type)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Receptors, Cell Surface)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Atherosclerosis/*chemically induced/pathology
MH  - Cell Adhesion Molecules/biosynthesis/genetics/*metabolism
MH  - Cytokines/biosynthesis
MH  - Endothelial Cells/*drug effects/*metabolism
MH  - Gene Knockdown Techniques
MH  - Human Umbilical Vein Endothelial Cells
MH  - Humans
MH  - Inflammation/*chemically induced/pathology
MH  - Intercellular Signaling Peptides and Proteins/*pharmacology
MH  - JNK Mitogen-Activated Protein Kinases/antagonists & inhibitors/*metabolism
MH  - Lectins, C-Type/genetics/*metabolism
MH  - Phosphorylation
MH  - Protein Kinase Inhibitors/pharmacology
MH  - RNA, Small Interfering/pharmacology
MH  - Receptors, Cell Surface/genetics/*metabolism
OTO - NOTNLM
OT  - Atherosclerosis
OT  - Inflammation
OT  - Leukocyte cell-derived chemotaxin 2
OT  - c-Jun N-terminal kinases
EDAT- 2015/07/01 06:00
MHDA- 2015/11/10 06:00
CRDT- 2015/07/01 06:00
PHST- 2015/03/03 00:00 [received]
PHST- 2015/05/12 00:00 [revised]
PHST- 2015/06/02 00:00 [accepted]
PHST- 2015/07/01 06:00 [entrez]
PHST- 2015/07/01 06:00 [pubmed]
PHST- 2015/11/10 06:00 [medline]
AID - S0026-0495(15)00162-6 [pii]
AID - 10.1016/j.metabol.2015.06.001 [doi]
PST - ppublish
SO  - Metabolism. 2015 Sep;64(9):1175-82. doi: 10.1016/j.metabol.2015.06.001. Epub 2015 
      Jun 6.