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. 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.

journal_name

Circulation

journal_title

Circulation

authors

Kempf VA,Lebiedziejewski M,Alitalo K,Wälzlein JH,Ehehalt U,Fiebig J,Huber S,Schütt B,Sander CA,Müller S,Grassl G,Yazdi AS,Brehm B,Autenrieth IB

doi

10.1161/01.CIR.0000155608.07691.B7

subject

Has Abstract

pub_date

2005-03-01 00:00:00

pages

1054-62

issue

8

eissn

0009-7322

issn

1524-4539

pii

01.CIR.0000155608.07691.B7

journal_volume

111

pub_type

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