HIF-1alpha mediates the induction of IL-8 and VEGF expression on infection with Afa/Dr diffusely adhering E. coli and promotes EMT-like behaviour. - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue Cellular Microbiology Année : 2009

HIF-1alpha mediates the induction of IL-8 and VEGF expression on infection with Afa/Dr diffusely adhering E. coli and promotes EMT-like behaviour.

Résumé

Summary Microbes regulate a large panel of intracellular signalling events that can promote inflammation and/or enhance tumour progression. Indeed, it has been shown that infection of human intestinal cells with the Afa/Dr diffusely adhering E. coli C1845 strain induces expression of pro-angiogenic and pro-inflammatory genes. Here, we demonstrate that exposure of cryptic-like intestinal epithelial cells to C1845 bacteria induces HIF-1alpha protein levels. This effect depends on the binding of F1845 adhesin to the membrane-associated DAF receptor that initiates signalling cascades promoting translational mechanisms. Indeed, inhibition of MAPK and PI-3K decreases HIF-1alpha protein levels and blocks C1845-induced phosphorylation of the ribosomal S6 protein. Using RNA interference we show that bacteria-induced HIF-1alpha regulates the expression of IL-8, VEGF and Twist1, thereby pointing to a role for HIF-1 in angiogenesis and inflammation. In addition, infection correlates with a loss of E-cadherin and cytokeratin 18 and a rise in fibronectin, suggesting that bacteria may induce an epithelial to mesenchymal transition-like phenotype. Since HIF-1alpha silencing results in reversion of bacteria-induced EMT markers, we speculate that HIF-1alpha plays a key role linking bacterial infection to angiogenesis, inflammation and some aspects of cancer initiation.

Dates et versions

hal-00457700 , version 1 (18-02-2010)

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Gaëlle Cane, Amandine Ginouvès, Sandrine Marchetti, Roser Buscà, Jacques Pouysségur, et al.. HIF-1alpha mediates the induction of IL-8 and VEGF expression on infection with Afa/Dr diffusely adhering E. coli and promotes EMT-like behaviour.. Cellular Microbiology, 2009, epub ahead of print. ⟨10.1111/j.1462-5822.2009.01422.x⟩. ⟨hal-00457700⟩
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