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 |
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Rok vydání: | 1997 |
Předmět: |
Cell type
medicine.medical_treatment Blotting Western Biophysics Biochemistry Interferon-gamma Mice Consensus Sequence medicine Animals Interferon gamma Endothelium RNA Messenger Cycloheximide Molecular Biology Transcription factor Binding Sites biology Tumor Necrosis Factor-alpha Effector Oligonucleotide NF-kappa B Brain Cell Biology Molecular biology Nitric oxide synthase Cytokine Gene Expression Regulation Oligodeoxyribonucleotides Mutation biology.protein Cytokines Tumor necrosis factor alpha Nitric Oxide Synthase medicine.drug |
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 |
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