RNA interference-produced autoregulation of inducible nitric oxide synthase expression

FEBS Lett. 2011 Aug 4;585(15):2488-92. doi: 10.1016/j.febslet.2011.06.032. Epub 2011 Jul 4.

Abstract

Vector-mediated delivery of short-hairpin RNA (shRNA) to regulate gene expression holds a great therapeutic promise. We hypothesize that gene expression can be autoregulated with RNA interference. We used inducible nitric oxide synthase (iNOS) as a gene model to test this hypothesis. Lipopolysaccharide dose-dependently increased iNOS in rat aortic smooth muscle cells and the nitrite production from these cells. These increases were attenuated in cells transfected with plasmids containing code for iNOS shRNA whose expression was controlled by an iNOS promoter. The production of shRNA was lipopolysaccharide dose-dependent. The lipopolysaccharide-induced iNOS expression in rat C6 glioma cells also was attenuated by transfection with plasmids containing the iNOS shRNA code. These results provide proof-of-concept evidence for using RNA interference technique to achieve autoregulation of gene expression.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aorta
  • Cell Line, Tumor
  • Gene Expression Regulation, Enzymologic
  • Glioma
  • Homeostasis* / drug effects
  • Lipopolysaccharides / pharmacology
  • Methods
  • Myocytes, Smooth Muscle / cytology
  • Myocytes, Smooth Muscle / metabolism
  • Nitric Oxide Synthase Type II / genetics*
  • Nitrites / metabolism
  • Plasmids / administration & dosage
  • RNA Interference / physiology*
  • RNA, Small Interfering / administration & dosage
  • RNA, Small Interfering / pharmacology*
  • Rats
  • Transfection

Substances

  • Lipopolysaccharides
  • Nitrites
  • RNA, Small Interfering
  • Nitric Oxide Synthase Type II
  • Nos2 protein, rat