Hauf N, Goebel W, Fiedler F, Sokolovic Z, Kuhn M
Theodor Boveri Institut für Biowissenschaften, Lehrstuhl für Mikrobiologie, Am Hubland, 97074 Würzburg, Germany.
Proc Natl Acad Sci U S A. 1997 Aug 19;94(17):9394-9. doi: 10.1073/pnas.94.17.9394.
As previously reported, Listeria monocytogenes infection of P388D1 macrophages results in a rapid induction of NF-kappaB DNA-binding activity. Here we show that this induction of NF-kappaB activity occurs in a biphasic mode: first, a transient, IkappaBalpha degradation-dependent phase of activity, also induced by the nonvirulent species Listeria innocua, which is mediated by binding of the bacteria to the macrophage, or by adding Listeria-derived lipoteichoic acid to the macrophage; the second persistent phase of activation is only markedly induced when the bacteria enter the cytoplasm of the host cell and express the virulence genes plcA and plcB, encoding two phospholipases. We suggest that products of the enzymatic activity of phospholipases directly interfere with host cell signal transduction pathways, thus leading to persistent NF-kappaB activation via persistent IkappaBbeta degradation.
如先前报道，单核细胞增生李斯特菌感染P388D1巨噬细胞会迅速诱导NF-κB DNA结合活性。在此我们表明，这种NF-κB活性的诱导以双相模式发生：首先，是一个短暂的、依赖IκBα降解的活性阶段，无毒李斯特菌也可诱导该阶段，它由细菌与巨噬细胞的结合介导，或通过向巨噬细胞添加李斯特菌来源的脂磷壁酸来诱导；第二个持续激活阶段只有在细菌进入宿主细胞胞质并表达编码两种磷脂酶的毒力基因plcA和plcB时才会明显诱导。我们认为磷脂酶的酶活性产物直接干扰宿主细胞信号转导途径，从而通过持续降解IκBβ导致NF-κB持续激活。
