@article{JesenbergerProcykRuethetal., author = {Jesenberger, Veronika and Procyk, Katarzyna and R{\"u}th, Jochen and Schreiber, Martin and Theussl, Hans Christian and Wagner, Erwin and Baccarini, Manuela}, title = {Protective Role of Raf-1 in Salmonella-Induced Macrophage Apoptosis}, series = {J Exp Med.}, volume = {2001}, journal = {J Exp Med.}, number = {193(3)}, doi = {10.1084/jem.193.3.353}, pages = {353 -- 364}, abstract = {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 κB 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.}, subject = {Salmonella-Induced Macrophage Apoptosis}, language = {en} }