title: Activation of hypoxia-inducible factor-1 in bacillary angiomatosis: evidence for a role of hypoxia-inducible factor-1 in bacterial infections.
abstract: BACKGROUND
  Bartonella species are the only known bacterial pathogens causing vasculoproliferative disorders in humans (bacillary angiomatosis [BA]). Cellular and bacterial pathogenetic mechanisms underlying the induction of BA are largely unknown.
  
  
  RESULTS
  Activation of hypoxia-inducible factor-1 (HIF-1), the key transcription factor involved in angiogenesis, was detected in Bartonella henselae-infected host cells in vitro by immunofluorescence, Western blotting, electrophoretic mobility shift, and reporter gene assays and by immunohistochemistry in BA tissue lesions in vivo. Gene microarray analysis revealed that a B henselae infection resulted in the activation of genes typical for the cellular response to hypoxia. HIF-1 was essential for B henselae-induced expression of vascular endothelial growth factor as shown by inhibition with the use of HIF-1-specific short-interfering RNA. Moreover, infection with B henselae resulted in increased oxygen consumption, cellular hypoxia, and decreased ATP levels in host cells. Infection with a pilus-negative variant of B henselae did not lead to cellular hypoxia or activation of HIF-1 or vascular endothelial growth factor secretion, suggesting a crucial role of this bacterial surface protein in the angiogenic reprogramming of the host cells.
  
  
  CONCLUSIONS
  B henselae induces a proangiogenic host cell response via HIF-1. Our data provide for the first time evidence that HIF-1 may play a role in bacterial infections.
authors.affiliation: Institut für Medizinische Mikrobiologie und Hygiene, Eberhard-Karls Universität, Tübingen, Germany. volkhard.kempf@med.uni-tuebingen.de
authors.forename: Volkhard A J
authors.initials: VA
authors.lastname: Kempf
authors.forename: Maria
authors.initials: M
authors.lastname: Lebiedziejewski
authors.forename: Kari
authors.initials: K
authors.lastname: Alitalo
authors.forename: Joo-Hee
authors.initials: JH
authors.lastname: Wälzlein
authors.forename: Urs
authors.initials: U
authors.lastname: Ehehalt
authors.forename: Jeannette
authors.initials: J
authors.lastname: Fiebig
authors.forename: Stephan
authors.initials: S
authors.lastname: Huber
authors.forename: Burkhardt
authors.initials: B
authors.lastname: Schütt
authors.forename: Christian A
authors.initials: CA
authors.lastname: Sander
authors.forename: Steffen
authors.initials: S
authors.lastname: Müller
authors.forename: Guntram
authors.initials: G
authors.lastname: Grassl
authors.forename: Amir S
authors.initials: AS
authors.lastname: Yazdi
authors.forename: Bernhard
authors.initials: B
authors.lastname: Brehm
authors.forename: Ingo B
authors.initials: IB
authors.lastname: Autenrieth
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D016917:Angiomatosis, Bacillary / Q000473:pathology*; D018416:Bartonella henselae / Q000302:isolation & purification / Q000472:pathogenicity; D015687:Cell Hypoxia / Q000502:physiology; D004268:DNA-Binding Proteins / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D042783:Endothelial Cells / Q000382:microbiology; D004730:Endothelium, Vascular / Q000166:cytology; D010861:Fimbriae, Bacterial / Q000378:metabolism / Q000502:physiology; D006367:HeLa Cells / Q000737:chemistry / Q000378:metabolism / Q000382:microbiology; D006644:Histiocytes / Q000737:chemistry / Q000473:pathology; D006801:Humans; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007150:Immunohistochemistry / Q000379:methods; D008264:Macrophages / Q000737:chemistry / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000382:microbiology; D009687:Nuclear Proteins / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D014157:Transcription Factors / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D014471:Umbilical Veins / Q000166:cytology; D015854:Up-Regulation / Q000502:physiology
chemical_list: D004268:DNA-Binding Proteins; C497442:HIF1A protein, human; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009687:Nuclear Proteins; D014157:Transcription Factors; D000255:Adenosine Triphosphate