Regulation of Cytokine-Induced iNOS Expression by a Hairpin Oligonucleotide in Murine Cerebral Endothelial Cells

Autor: Chung Y. Hsu, Jan Xu, Yanquing Yang, Steven A. Moore, Yingji Wu, Luming He
Rok vydání: 1997
Předmět:
Zdroj: Biochemical and Biophysical Research Communications. 235:394-397
ISSN: 0006-291X
DOI: 10.1006/bbrc.1997.6800
Popis: Inducible nitric oxide synthase (iNOS) is expressed in response to cytokines by a number of cell types participating in CNS inflammation, including brain cerebral endothelial cells. NF-kappaB, a transcription factor, mediates effector actions of pro-inflammatory cytokines. A combination of tumor necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma) enhanced the expression of iNOS in murine cerebral endothelial cells (MCECs). In an attempt to modulate TNF-alpha+IFN-gamma induced expression of iNOS in MCECs, we designed a double-strand hairpin (hp) oligonucleotide carrying the NF-kappaB motif. This hp oligonucleotide inhibited NF-kappaB binding activity and decreased both iNOS mRNA and protein expression induced by TNF-alpha+IFN-gamma. As a control, a mutant hp oligonucleotide was without effect. The present study confirms the role of transcription factor NF-kappaB in iNOS expression induced by TNF-alpha+IFN-gamma in MCECs. More importantly, it demonstrates that an appropriately designed hp oligonucleotide is an effective tool to modulate iNOS expression and may be of potential pharmacological use.
Databáze: OpenAIRE