title: Antisense RNA to inducible nitric oxide synthase reduces cytokine-mediated brain endothelial cell death.
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-alpha (TNF-alpha) plus interferon-gamma (IFN-gamma), 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.
authors.affiliation: Institute of Neuroscience, Tzu Chi University, Hualien, Taiwan.
authors.forename: Ding-I
authors.initials: DI
authors.lastname: Yang
authors.forename: Shawei
authors.initials: S
authors.lastname: Chen
authors.forename: Uthayashanker R
authors.initials: UR
authors.lastname: Ezekiel
authors.forename: Jan
authors.initials: J
authors.lastname: Xu
authors.forename: Yingji
authors.initials: Y
authors.lastname: Wu
authors.forename: Chung Y
authors.initials: CY
authors.lastname: Hsu
mesh_terms: D000818:Animals; D001921:Brain / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D016207:Cytokines / Q000494:pharmacology*; D042783:Endothelial Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism*; D016372:RNA, Antisense / Q000235:genetics*
chemical_list: D016207:Cytokines; D016372:RNA, Antisense; D052247:Nitric Oxide Synthase Type II