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Antisense RNA to Inducible Nitric Oxide Synthase Reduces Cytokine‐Mediated Brain Endothelial Cell Death
Author(s) -
YANG DINGI,
CHEN SHAWEI,
EZEKIEL UTHAYASHANKER R.,
XU JAN,
WU YINGJI,
HSU CHUNG Y.
Publication year - 2005
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1338.037
Subject(s) - nitric oxide synthase , antisense rna , sense (electronics) , nitric oxide , endothelium , endothelial stem cell , tumor necrosis factor alpha , cytotoxic t cell , transfection , microbiology and biotechnology , chemistry , cytokine , stimulation , biology , cell culture , rna , immunology , biochemistry , in vitro , endocrinology , genetics , gene
A bstract : 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.