PMID- 15723970 OWN - NLM STAT- MEDLINE DCOM- 20050930 LR - 20220309 IS - 1524-4539 (Electronic) IS - 0009-7322 (Linking) VI - 111 IP - 8 DP - 2005 Mar 1 TI - Activation of hypoxia-inducible factor-1 in bacillary angiomatosis: evidence for a role of hypoxia-inducible factor-1 in bacterial infections. PG - 1054-62 AB - 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. METHODS AND 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. FAU - Kempf, Volkhard A J AU - Kempf VA AD - Institut fur Medizinische Mikrobiologie und Hygiene, Eberhard-Karls Universitat, Tubingen, Germany. volkhard.kempf@med.uni-tuebingen.de FAU - Lebiedziejewski, Maria AU - Lebiedziejewski M FAU - Alitalo, Kari AU - Alitalo K FAU - Walzlein, Joo-Hee AU - Walzlein JH FAU - Ehehalt, Urs AU - Ehehalt U FAU - Fiebig, Jeannette AU - Fiebig J FAU - Huber, Stephan AU - Huber S FAU - Schutt, Burkhardt AU - Schutt B FAU - Sander, Christian A AU - Sander CA FAU - Muller, Steffen AU - Muller S FAU - Grassl, Guntram AU - Grassl G FAU - Yazdi, Amir S AU - Yazdi AS FAU - Brehm, Bernhard AU - Brehm B FAU - Autenrieth, Ingo B AU - Autenrieth IB LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20050221 PL - United States TA - Circulation JT - Circulation JID - 0147763 RN - 0 (DNA-Binding Proteins) RN - 0 (HIF1A protein, human) RN - 0 (Hypoxia-Inducible Factor 1) RN - 0 (Hypoxia-Inducible Factor 1, alpha Subunit) RN - 0 (Nuclear Proteins) RN - 0 (Transcription Factors) RN - 8L70Q75FXE (Adenosine Triphosphate) SB - IM MH - Adenosine Triphosphate/metabolism MH - Angiomatosis, Bacillary/*pathology MH - Bartonella henselae/isolation & purification/pathogenicity MH - Cell Hypoxia/physiology MH - DNA-Binding Proteins/immunology/metabolism/*physiology MH - Endothelial Cells/microbiology MH - Endothelium, Vascular/cytology MH - Fimbriae, Bacterial/metabolism/physiology MH - HeLa Cells/chemistry/metabolism/microbiology MH - Histiocytes/chemistry/pathology MH - Humans MH - Hypoxia-Inducible Factor 1 MH - Hypoxia-Inducible Factor 1, alpha Subunit MH - Immunohistochemistry/methods MH - Macrophages/chemistry/pathology MH - Neovascularization, Pathologic/microbiology MH - Nuclear Proteins/immunology/metabolism/*physiology MH - Transcription Factors/immunology/metabolism/*physiology MH - Umbilical Veins/cytology MH - Up-Regulation/physiology EDAT- 2005/02/23 09:00 MHDA- 2005/10/01 09:00 CRDT- 2005/02/23 09:00 PHST- 2005/02/23 09:00 [pubmed] PHST- 2005/10/01 09:00 [medline] PHST- 2005/02/23 09:00 [entrez] AID - 01.CIR.0000155608.07691.B7 [pii] AID - 10.1161/01.CIR.0000155608.07691.B7 [doi] PST - ppublish SO - Circulation. 2005 Mar 1;111(8):1054-62. doi: 10.1161/01.CIR.0000155608.07691.B7. Epub 2005 Feb 21.