PMID: 18212534Jan 24, 2008Paper

Synergystic induction of HIF-1alpha transcriptional activity by hypoxia and lipopolysaccharide in macrophages

Cell Cycle
Zenghui MiL Varesio

Abstract

Hypoxia Inducible Factor-1 (HIF-1) is activated by a variety of stimuli, including inflammatory mediators. In this report we investigated the role that bacterial lipopolysaccharide (LPS) and hypoxia play in the regulation of HIF-1-dependent gene expression in macrophages. We report that murine macrophages stimulated with low concentrations of LPS (1-10 ng/ml) expressed significantly higher levels of inducible nitric oxide synthase (iNOS) mRNA when cultured under hypoxic compared to normoxic conditions. Functional studies of the iNOS promoter demonstrated that the synergistic interaction between LPS and hypoxia was mediated, at least in part, by the NFkappaB and the HIF-1 binding sites. In addition, transient transfection experiments using a Hypoxia Response Element (HRE)-containing plasmid showed that LPS and hypoxia synergistically induced HIF-1-dependent transcriptional activity. Interestingly, LPS did not significantly affect HIF-1alpha protein levels or HIF-1 DNA binding activity relative to hypoxic induction. HIF-1alpha, but not HIF-2alpha, was critical for the synergistic induction of HRE-dependent transcriptional activity in macrophages, as indicated by experiments using siRNA targeting HIF-1alpha or HIF-2alpha. Addition...Continue Reading

Citations

Mar 20, 2010·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·A C BrooksJ Elliott
Apr 22, 2009·Molecular BioSystems·Valerie HowerSuzy V Torti
Oct 4, 2008·Toxicological Sciences : an Official Journal of the Society of Toxicology·Kelly A Brant, James P Fabisiak
Oct 1, 2011·Free Radical Biology & Medicine·Mary A RobinsonCynthia M Otto
Dec 29, 2010·Biochemical and Biophysical Research Communications·Daniela B S MendonçaLyndon F Cooper
Sep 12, 2009·Liver International : Official Journal of the International Association for the Study of the Liver·Tomas RegueiraSiamak Djafarzadeh
Aug 21, 2012·Immunobiology·Maria Carla Bosco, Luigi Varesio
Sep 19, 2009·Arteriosclerosis, Thrombosis, and Vascular Biology·Kotaro TakedaKenji Sunagawa
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Aug 26, 2009·Nature Reviews. Immunology·Victor Nizet, Randall S Johnson
Apr 25, 2019·Basic Research in Cardiology·Bernadin Ndongson-DongmoReinhard Bauer
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Mar 9, 2019·American Journal of Respiratory and Critical Care Medicine·Alison J HarrisSarah R Walmsley
Aug 28, 2019·International Journal of Molecular Sciences·Laurent M PaardekooperGeert van den Bogaart
Feb 24, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Bárbara Acosta-IborraManuel O Landázuri
Jul 18, 2021·European Journal of Immunology·Federica PiattiniManfred Kopf

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