Activation of hypoxia-inducible factor-1 in bacillary angiomatosis: evidence for a role of hypoxia-inducible factor-1 in bacterial infections - PubMed (original) (raw)
. 2005 Mar 1;111(8):1054-62.
doi: 10.1161/01.CIR.0000155608.07691.B7. Epub 2005 Feb 21.
Maria Lebiedziejewski, Kari Alitalo, Joo-Hee Wälzlein, Urs Ehehalt, Jeannette Fiebig, Stephan Huber, Burkhardt Schütt, Christian A Sander, Steffen Müller, Guntram Grassl, Amir S Yazdi, Bernhard Brehm, Ingo B Autenrieth
Affiliations
- PMID: 15723970
- DOI: 10.1161/01.CIR.0000155608.07691.B7
Activation of hypoxia-inducible factor-1 in bacillary angiomatosis: evidence for a role of hypoxia-inducible factor-1 in bacterial infections
Volkhard A J Kempf et al. Circulation. 2005.
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.
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.
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