Inhibition by the JAK/STAT pathway of IFNgamma- and LPS-stimulated nitric oxide synthase induction in vascular smooth muscle cells

Biochem Biophys Res Commun. 1998 Nov 18;252(2):508-12. doi: 10.1006/bbrc.1998.9678.

Abstract

Inducible nitric oxide synthase (iNOS) is induced in many cell types by cytokines and lipopolysaccharide (LPS). Cytokine signal transduction is believed to be mediated primarily through the JAK/STAT pathway. We therefore examined the effects of a JAK2-specific inhibitor, an antisense oligonucleotide to JAK2, and electroporation of neutralizing anti-STAT1 and anti-STAT3 antibodies on IFNgamma- and LPS-stimulated induction of iNOS in vascular smooth muscle cells. Unexpectedly, we found that the JAK/STAT pathway suppresses IFNgamma- and LPS-stimulated iNOS induction in these cells. In contrast, the JAK/STAT pathway appears to have a positive role in iNOS induction in RAW 264.7 macrophages.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Base Sequence
  • Cells, Cultured
  • DNA-Binding Proteins / metabolism
  • Enzyme Induction / drug effects
  • Interferon-gamma / pharmacology*
  • Janus Kinase 2
  • Lipopolysaccharides / pharmacology*
  • Muscle, Smooth, Vascular / drug effects*
  • Muscle, Smooth, Vascular / enzymology*
  • Nitric Oxide Synthase / biosynthesis*
  • Nitric Oxide Synthase Type II
  • Oligodeoxyribonucleotides / genetics
  • Protein-Tyrosine Kinases / genetics
  • Protein-Tyrosine Kinases / metabolism
  • Proto-Oncogene Proteins*
  • Rats
  • Recombinant Proteins
  • STAT1 Transcription Factor
  • STAT3 Transcription Factor
  • Signal Transduction
  • Trans-Activators / metabolism

Substances

  • DNA-Binding Proteins
  • Lipopolysaccharides
  • Oligodeoxyribonucleotides
  • Proto-Oncogene Proteins
  • Recombinant Proteins
  • STAT1 Transcription Factor
  • STAT3 Transcription Factor
  • Stat1 protein, rat
  • Stat3 protein, rat
  • Trans-Activators
  • Interferon-gamma
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II
  • Nos2 protein, rat
  • Protein-Tyrosine Kinases
  • Jak2 protein, rat
  • Janus Kinase 2