Conditional expression of microRNA against E-selectin inhibits leukocyte-endothelial adhesive interaction under inflammatory condition

Kaichi Yoshizaki, Hideaki Wakita, Kazuya Takeda, Keikichi Takahashi

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Human E-selectin, an endothelial adhesion molecule, is induced in the brain arteries by cerebral ischemia and participates in the infiltration of leukocytes that cause inflammatory reaction leading to brain damage. To prevent leukocyte infiltration in the brain, we designed gene therapeutic constructs to suppress E-selectin expression. The constructs were composed of microRNAs (miR-E1 and miR-E2) complementary to the human E-selectin cDNA, which were directed by a minimum cis-element of the human E-selectin promoter. Transfection in human aorta endothelial cells (HAECs) with these constructs revealed that the E-selectin promoter was sufficiently activated in response to tumor necrosis factor-α (TNF-α), and miR-E1 and miR-E2 could suppress E-selectin expression resulting in the significant inhibition of leukocyte adhesion. These results suggested that the combination of the E-selectin promoter and microRNAs could allow the restricted expression of transgenes in activated endothelial cells and diminish leukocyte recruitment.

Original languageEnglish
Pages (from-to)747-751
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume371
Issue number4
DOIs
Publication statusPublished - 11-07-2008

Fingerprint

E-Selectin
MicroRNAs
Adhesives
Leukocytes
Brain
Endothelial cells
Infiltration
Adhesion
Endothelial Cells
Brain Ischemia
Transgenes
Transfection
Aorta
Complementary DNA
Arteries
Tumor Necrosis Factor-alpha
Genes
Molecules
human SELE protein
Therapeutics

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

@article{dd1da317e7e74bf08e60d8caa4039016,
title = "Conditional expression of microRNA against E-selectin inhibits leukocyte-endothelial adhesive interaction under inflammatory condition",
abstract = "Human E-selectin, an endothelial adhesion molecule, is induced in the brain arteries by cerebral ischemia and participates in the infiltration of leukocytes that cause inflammatory reaction leading to brain damage. To prevent leukocyte infiltration in the brain, we designed gene therapeutic constructs to suppress E-selectin expression. The constructs were composed of microRNAs (miR-E1 and miR-E2) complementary to the human E-selectin cDNA, which were directed by a minimum cis-element of the human E-selectin promoter. Transfection in human aorta endothelial cells (HAECs) with these constructs revealed that the E-selectin promoter was sufficiently activated in response to tumor necrosis factor-α (TNF-α), and miR-E1 and miR-E2 could suppress E-selectin expression resulting in the significant inhibition of leukocyte adhesion. These results suggested that the combination of the E-selectin promoter and microRNAs could allow the restricted expression of transgenes in activated endothelial cells and diminish leukocyte recruitment.",
author = "Kaichi Yoshizaki and Hideaki Wakita and Kazuya Takeda and Keikichi Takahashi",
year = "2008",
month = "7",
day = "11",
doi = "10.1016/j.bbrc.2008.04.160",
language = "English",
volume = "371",
pages = "747--751",
journal = "Biochemical and Biophysical Research Communications",
issn = "0006-291X",
publisher = "Academic Press Inc.",
number = "4",

}

Conditional expression of microRNA against E-selectin inhibits leukocyte-endothelial adhesive interaction under inflammatory condition. / Yoshizaki, Kaichi; Wakita, Hideaki; Takeda, Kazuya; Takahashi, Keikichi.

In: Biochemical and Biophysical Research Communications, Vol. 371, No. 4, 11.07.2008, p. 747-751.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Conditional expression of microRNA against E-selectin inhibits leukocyte-endothelial adhesive interaction under inflammatory condition

AU - Yoshizaki, Kaichi

AU - Wakita, Hideaki

AU - Takeda, Kazuya

AU - Takahashi, Keikichi

PY - 2008/7/11

Y1 - 2008/7/11

N2 - Human E-selectin, an endothelial adhesion molecule, is induced in the brain arteries by cerebral ischemia and participates in the infiltration of leukocytes that cause inflammatory reaction leading to brain damage. To prevent leukocyte infiltration in the brain, we designed gene therapeutic constructs to suppress E-selectin expression. The constructs were composed of microRNAs (miR-E1 and miR-E2) complementary to the human E-selectin cDNA, which were directed by a minimum cis-element of the human E-selectin promoter. Transfection in human aorta endothelial cells (HAECs) with these constructs revealed that the E-selectin promoter was sufficiently activated in response to tumor necrosis factor-α (TNF-α), and miR-E1 and miR-E2 could suppress E-selectin expression resulting in the significant inhibition of leukocyte adhesion. These results suggested that the combination of the E-selectin promoter and microRNAs could allow the restricted expression of transgenes in activated endothelial cells and diminish leukocyte recruitment.

AB - Human E-selectin, an endothelial adhesion molecule, is induced in the brain arteries by cerebral ischemia and participates in the infiltration of leukocytes that cause inflammatory reaction leading to brain damage. To prevent leukocyte infiltration in the brain, we designed gene therapeutic constructs to suppress E-selectin expression. The constructs were composed of microRNAs (miR-E1 and miR-E2) complementary to the human E-selectin cDNA, which were directed by a minimum cis-element of the human E-selectin promoter. Transfection in human aorta endothelial cells (HAECs) with these constructs revealed that the E-selectin promoter was sufficiently activated in response to tumor necrosis factor-α (TNF-α), and miR-E1 and miR-E2 could suppress E-selectin expression resulting in the significant inhibition of leukocyte adhesion. These results suggested that the combination of the E-selectin promoter and microRNAs could allow the restricted expression of transgenes in activated endothelial cells and diminish leukocyte recruitment.

UR - http://www.scopus.com/inward/record.url?scp=44149114225&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=44149114225&partnerID=8YFLogxK

U2 - 10.1016/j.bbrc.2008.04.160

DO - 10.1016/j.bbrc.2008.04.160

M3 - Article

C2 - 18471997

AN - SCOPUS:44149114225

VL - 371

SP - 747

EP - 751

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

SN - 0006-291X

IS - 4

ER -