LECT2 induces atherosclerotic inflammatory reaction via CD209 receptor-mediated JNK phosphorylation in human endothelial cells

Hwan Jin Hwang, Tae Woo Jung, Ho Cheol Hong, Ji A Seo, Sin Gon Kim, Nan Hee Kim, Kyung Mook Choi, Dong Seop Choi, Sei-Hyun Baik, Hye-Jin Yoo

Research output: Contribution to journalArticle

18 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1175-1182
Number of pages8
JournalMetabolism: Clinical and Experimental
Volume64
Issue number9
DOIs
Publication statusPublished - 2015 Jan 1

Fingerprint

JNK Mitogen-Activated Protein Kinases
Chemotactic Factors
Leukocytes
Endothelial Cells
Phosphorylation
Human Umbilical Vein Endothelial Cells
Cytokines
Intercellular Adhesion Molecule-1
Interleukin-1
Cell Adhesion
Small Interfering RNA
Blood Vessels
Insulin Resistance
Real-Time Polymerase Chain Reaction
Monocytes
Skeletal Muscle
Tumor Necrosis Factor-alpha
Western Blotting

Keywords

  • Atherosclerosis
  • c-Jun N-terminal kinases
  • Inflammation
  • Leukocyte cell-derived chemotaxin 2

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

@article{980bfe3581ae476d8676d0f92b0b2d91,
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.",
keywords = "Atherosclerosis, c-Jun N-terminal kinases, Inflammation, Leukocyte cell-derived chemotaxin 2",
author = "Hwang, {Hwan Jin} and Jung, {Tae Woo} and Hong, {Ho Cheol} and Seo, {Ji A} and Kim, {Sin Gon} and Kim, {Nan Hee} and Choi, {Kyung Mook} and Choi, {Dong Seop} and Sei-Hyun Baik and Hye-Jin Yoo",
year = "2015",
month = "1",
day = "1",
doi = "10.1016/j.metabol.2015.06.001",
language = "English",
volume = "64",
pages = "1175--1182",
journal = "Metabolism: Clinical and Experimental",
issn = "0026-0495",
publisher = "W.B. Saunders Ltd",
number = "9",

}

TY - JOUR

T1 - LECT2 induces atherosclerotic inflammatory reaction via CD209 receptor-mediated JNK phosphorylation in human endothelial cells

AU - Hwang, Hwan Jin

AU - Jung, Tae Woo

AU - Hong, Ho Cheol

AU - Seo, Ji A

AU - Kim, Sin Gon

AU - Kim, Nan Hee

AU - Choi, Kyung Mook

AU - Choi, Dong Seop

AU - Baik, Sei-Hyun

AU - Yoo, Hye-Jin

PY - 2015/1/1

Y1 - 2015/1/1

N2 - 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.

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 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.

KW - Atherosclerosis

KW - c-Jun N-terminal kinases

KW - Inflammation

KW - Leukocyte cell-derived chemotaxin 2

UR - http://www.scopus.com/inward/record.url?scp=84939563917&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84939563917&partnerID=8YFLogxK

U2 - 10.1016/j.metabol.2015.06.001

DO - 10.1016/j.metabol.2015.06.001

M3 - Article

C2 - 26123523

AN - SCOPUS:84939563917

VL - 64

SP - 1175

EP - 1182

JO - Metabolism: Clinical and Experimental

JF - Metabolism: Clinical and Experimental

SN - 0026-0495

IS - 9

ER -