PMID: 7520478Sep 1, 1994Paper

Role of interferon regulatory factor 1 in induction of nitric oxide synthase

The Journal of Experimental Medicine
E MartinQ W Xie

Abstract

Interferon gamma (IFN-gamma) interacts synergistically with bacterial lipopolysaccharide (LPS) to induce transcription of iNOS, the isoform of nitric oxide synthase whose activity is independent of elevated Ca2+ and exogenous calmodulin. To define a cis-acting element mediating IFN-gamma-dependent synergy, we made deletions in iNOS promoter constructs fused to reporter genes, transfected RAW 264.7 macrophages, and treated the cells with IFN-gamma and/or LPS. This analysis implicated the region from positions -951 to -911, a cluster of four enhancer elements known to bind IFN-gamma-responsive transcription factors, including an interferon regulatory factor binding site (IRF-E) at nucleotides -913 to -923. Site-specific substitution of two conserved nucleotides within IRF-E in the context of the full-length iNOS promoter ablated IFN-gamma's contribution to synergistic enhancement of transcription. Electromobility shift assays performed with a probe containing IRF-E revealed the existence of a complex in nuclei of RAW 264.7 macrophages that was present only after treatment with IFN-gamma, which reacted specifically with anti-IRF-1 immunoglobulin G and which included a species migrating at 40-45 kD, consistent with the apparent mol...Continue Reading

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Citations

Aug 24, 2000·International Journal of Cancer. Journal International Du Cancer·H Xi, G Blanck
Feb 19, 2000·Biochemical and Biophysical Research Communications·Y HongN Yamada
Jan 1, 1994·Journal of Molecular Neuroscience : MN·J R Sparrow
May 24, 2005·Digestive Diseases and Sciences·Naoki HirabayashiHiroki Yamaue
Apr 12, 2008·Purinergic Signalling·Alma N GuerraPaul J Bertics
Mar 7, 2012·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Benjamin B GelmanVicki M Soukup
Oct 11, 2003·Pharmacology & Therapeutics·Dhananjaya V Kalvakolanu
Mar 1, 1997·Trends in Neurosciences·C Iadecola
Jan 25, 2003·Burns : Journal of the International Society for Burn Injuries·Martin G Schwacha
Apr 10, 2003·Free Radical Biology & Medicine·Keping Xie, Suyun Huang
Aug 5, 2003·Nitric Oxide : Biology and Chemistry·Aaron T Jacobs, Louis J Ignarro
Aug 26, 2000·Cytokine & Growth Factor Reviews·A DenkB Baumann
Jun 10, 1998·Cytokine & Growth Factor Reviews·H NguyenP M Pitha
May 30, 1998·British Journal of Pharmacology·H KleinertU Förstermann

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