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

Kaichi Yoshizaki, Hideaki Wakita, Kazuya Takeda, Keikichi Takahashi

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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

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All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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