Protective role of Raf-1 in Salmonella-induced macrophage apoptosis

Autor(en)

Veronika Jesenberger, Katarzyna J. Procyk, Jochen Rüth, Martin Schreiber, Hans Christian Theussl, Erwin Friedrich Wagner, Manuela Baccarini

Abstrakt

Invasive Salmonella induces macrophage apoptosis via the activation of caspase-1 by the bacterial protein SipB. Here we show that infection of macrophages with Salmonella causes the activation and degradation of Raf-1, an important intermediate in macrophage proliferation and activation. Raf-1 degradation is SipB- and caspase-1-dependent, and is prevented by proteasome inhibitors. To study the functional significance of Raf-1 in this process, the c-raf-1 gene was inactivated by Cre-loxP-mediated recombination in vivo. Macrophages lacking c-raf-1 are hypersensitive towards pathogen-induced apoptosis. Surprisingly, activation of the antiapoptotic mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) and nuclear factor ?B pathways is normal in Raf-1-deficient macrophages, and mitochondrial fragility is not increased. Instead, pathogen-mediated activation of caspase-1 is enhanced selectively, implying that Raf-1 antagonizes stimulus-induced caspase-1 activation and apoptosis.

Organisation(en)

Externe Organisation(en)

Cancer Research UK, Karl-Franzens-Universität Graz, Vienna BioCenter

Journal

The Journal of Experimental Medicine

Band

193

Seiten

353-364

Anzahl der Seiten

12

ISSN

0022-1007

Publikationsdatum

2001

Peer-reviewed

Ja

ÖFOS 2012

1060 Biologie

Link zum Portal

https://ucrisportal.univie.ac.at/de/publications/protective-role-of-raf1-in-salmonellainduced-macrophage-apoptosis(0a7dc232-30f7-446d-84a8-e2a2e880d9ab).html