Protective role of Raf-1 in Salmonella-induced macrophage apoptosis.
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 kappaB 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.[1]References
- Protective role of Raf-1 in Salmonella-induced macrophage apoptosis. Jesenberger, V., Procyk, K.J., Rüth, J., Schreiber, M., Theussl, H.C., Wagner, E.F., Baccarini, M. J. Exp. Med. (2001) [Pubmed]
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