Antisense RNA to inducible nitric oxide synthase reduces cytokine-mediated brain endothelial cell death

Ding I. Yang, Shawei Chen, Uthayashanker R. Ezekiel, Jan Xu, Yingji Wu, Chung Y. Hsu

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

We test whether inhibition of inducible nitric oxide synthase (iNOS) can exert a cytoprotective effect on cerebral endothelial cells upon stimulation by pro-inflammatory cytokines. Mouse brain endothelial cells were stably transfected to express an antisense RNA against iNOS driven by an endothelium-specific von Willebrand factor (vWF) promoter. Upon stimulation with tumor necrosis factor-α (TNF-α) plus interferon-γ (IFN-γ), antisense transfectants showed less iNOS enzymatic activity with less nitric oxide (NO) when compared to the sense control cells. Correspondingly, the antisense cells showed a reduced LDH release and less cytosolic content of oligonucleosomes. These findings establish a cell-specific antisense strategy and confirm the cytotoxic role of iNOS expression in cultured cerebral endothelial cells.

Original languageEnglish
Pages (from-to)439-447
Number of pages9
JournalAnnals of the New York Academy of Sciences
Volume1042
DOIs
Publication statusPublished - 2005

Keywords

  • Endothelial cells
  • Interferon-γ
  • Tumor necrosis factor-α
  • Von Willebrand factor

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

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