Cardiotrophin-1 stimulates intercellular adhesion molecule-1 and monocyte chemoattractant protein-1 in human aortic endothelial cells

Tomoko Ichiki, Michihisa Jougasaki, Manabu Setoguchi, Junichi Imamura, Hitoshi Nakashima, Tatsuru Matsuoka, Masahiro Sonoda, Kazuhiko Nakamura, Shinichi Minagoe, Chuwa Tei

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Intercellular adhesion molecule-1 (ICAM-1) and monocyte chemoattractant protein-1 (MCP-1) play critical roles in mediating monocyte adhesion to the vascular endothelium and monocyte migration into the subendothelial regions of the vessels. Inasmuch as cardiotrophin-1 (CT-1), an IL-6-type cytokine, was expressed in human atherosclerotic plaque, we examined whether CT-1 induces monocyte adhesion and migration by stimulating gene and protein expressions of ICAM-1 and MCP-1 in human aortic endothelial cells (HAECs). Immunocytochemistry revealed that CT-1 increased intensity of ICAM-1 and MCP-1 immunoreactivity in HAECs. Adhesion assay and chemotaxis assay revealed that CT-1 increased human monocytic THP-1 cell adhesion to HAECs and promoted chemotaxis in THP-1 cells, which were attenuated by anti-ICAM-1 and anti-MCP-1 antibody, respectively. Western blot analysis showed that CT-1 increased phosphorylation of ERK1/2 MAP kinase, p38 MAP kinase, and Akt and that their inhibitors, PD-98059, SB-203580, and LY-294002, respectively, inhibited phosphorylation. RNase protection assay and ELISA demonstrated that CT-1 increased gene and protein expressions of ICAM-1 and MCP-1. EMSA revealed that CT-1 enhanced NF-κB DNA-binding activity. CT-1-mediated upregulation of ICAM-1 and MCP-1 was suppressed by PD-98059, SB-203580, LY-294002, and parthenolide. The present study demonstrates that CT-1 promotes monocyte adhesion and migration by stimulating ICAM-1 and MCP-1 through mechanisms that involve ERK1/2 MAP kinase, p38 MAP kinase, phosphatidylinositol 3-kinase, and NF-κB pathways and suggests that CT-1 plays an important role in the pathophysiology of vascular inflammation and atherosclerosis.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume294
Issue number2
DOIs
StatePublished - Feb 2008
Externally publishedYes

Fingerprint

Intercellular Adhesion Molecule-1
Endothelial Cells
Chemokine CCL2
Monocytes
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Mitogen-Activated Protein Kinase Kinases
p38 Mitogen-Activated Protein Kinases
Chemotaxis
Phosphorylation
human CCL2 protein
cardiotrophin 1
Phosphatidylinositol 3-Kinase
Gene Expression
Vascular Endothelium
Atherosclerotic Plaques
Ribonucleases
Cell Adhesion
Blood Vessels
Interleukin-6
Atherosclerosis

Keywords

  • Atherosclerosis
  • Vascular inflammation

ASJC Scopus subject areas

  • Physiology

Cite this

Cardiotrophin-1 stimulates intercellular adhesion molecule-1 and monocyte chemoattractant protein-1 in human aortic endothelial cells. / Ichiki, Tomoko; Jougasaki, Michihisa; Setoguchi, Manabu; Imamura, Junichi; Nakashima, Hitoshi; Matsuoka, Tatsuru; Sonoda, Masahiro; Nakamura, Kazuhiko; Minagoe, Shinichi; Tei, Chuwa.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 294, No. 2, 02.2008.

Research output: Contribution to journalArticle

Ichiki, Tomoko ; Jougasaki, Michihisa ; Setoguchi, Manabu ; Imamura, Junichi ; Nakashima, Hitoshi ; Matsuoka, Tatsuru ; Sonoda, Masahiro ; Nakamura, Kazuhiko ; Minagoe, Shinichi ; Tei, Chuwa. / Cardiotrophin-1 stimulates intercellular adhesion molecule-1 and monocyte chemoattractant protein-1 in human aortic endothelial cells. In: American Journal of Physiology - Heart and Circulatory Physiology. 2008 ; Vol. 294, No. 2.
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abstract = "Intercellular adhesion molecule-1 (ICAM-1) and monocyte chemoattractant protein-1 (MCP-1) play critical roles in mediating monocyte adhesion to the vascular endothelium and monocyte migration into the subendothelial regions of the vessels. Inasmuch as cardiotrophin-1 (CT-1), an IL-6-type cytokine, was expressed in human atherosclerotic plaque, we examined whether CT-1 induces monocyte adhesion and migration by stimulating gene and protein expressions of ICAM-1 and MCP-1 in human aortic endothelial cells (HAECs). Immunocytochemistry revealed that CT-1 increased intensity of ICAM-1 and MCP-1 immunoreactivity in HAECs. Adhesion assay and chemotaxis assay revealed that CT-1 increased human monocytic THP-1 cell adhesion to HAECs and promoted chemotaxis in THP-1 cells, which were attenuated by anti-ICAM-1 and anti-MCP-1 antibody, respectively. Western blot analysis showed that CT-1 increased phosphorylation of ERK1/2 MAP kinase, p38 MAP kinase, and Akt and that their inhibitors, PD-98059, SB-203580, and LY-294002, respectively, inhibited phosphorylation. RNase protection assay and ELISA demonstrated that CT-1 increased gene and protein expressions of ICAM-1 and MCP-1. EMSA revealed that CT-1 enhanced NF-κB DNA-binding activity. CT-1-mediated upregulation of ICAM-1 and MCP-1 was suppressed by PD-98059, SB-203580, LY-294002, and parthenolide. The present study demonstrates that CT-1 promotes monocyte adhesion and migration by stimulating ICAM-1 and MCP-1 through mechanisms that involve ERK1/2 MAP kinase, p38 MAP kinase, phosphatidylinositol 3-kinase, and NF-κB pathways and suggests that CT-1 plays an important role in the pathophysiology of vascular inflammation and atherosclerosis.",
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AU - Imamura, Junichi

AU - Nakashima, Hitoshi

AU - Matsuoka, Tatsuru

AU - Sonoda, Masahiro

AU - Nakamura, Kazuhiko

AU - Minagoe, Shinichi

AU - Tei, Chuwa

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AB - Intercellular adhesion molecule-1 (ICAM-1) and monocyte chemoattractant protein-1 (MCP-1) play critical roles in mediating monocyte adhesion to the vascular endothelium and monocyte migration into the subendothelial regions of the vessels. Inasmuch as cardiotrophin-1 (CT-1), an IL-6-type cytokine, was expressed in human atherosclerotic plaque, we examined whether CT-1 induces monocyte adhesion and migration by stimulating gene and protein expressions of ICAM-1 and MCP-1 in human aortic endothelial cells (HAECs). Immunocytochemistry revealed that CT-1 increased intensity of ICAM-1 and MCP-1 immunoreactivity in HAECs. Adhesion assay and chemotaxis assay revealed that CT-1 increased human monocytic THP-1 cell adhesion to HAECs and promoted chemotaxis in THP-1 cells, which were attenuated by anti-ICAM-1 and anti-MCP-1 antibody, respectively. Western blot analysis showed that CT-1 increased phosphorylation of ERK1/2 MAP kinase, p38 MAP kinase, and Akt and that their inhibitors, PD-98059, SB-203580, and LY-294002, respectively, inhibited phosphorylation. RNase protection assay and ELISA demonstrated that CT-1 increased gene and protein expressions of ICAM-1 and MCP-1. EMSA revealed that CT-1 enhanced NF-κB DNA-binding activity. CT-1-mediated upregulation of ICAM-1 and MCP-1 was suppressed by PD-98059, SB-203580, LY-294002, and parthenolide. The present study demonstrates that CT-1 promotes monocyte adhesion and migration by stimulating ICAM-1 and MCP-1 through mechanisms that involve ERK1/2 MAP kinase, p38 MAP kinase, phosphatidylinositol 3-kinase, and NF-κB pathways and suggests that CT-1 plays an important role in the pathophysiology of vascular inflammation and atherosclerosis.

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