Institute of Clinical Molecular Biology, Christian Albrechts University, Kiel D-24105, Germany.
J Biol Chem. 2010 Jun 25;285(26):19921-6. doi: 10.1074/jbc.M110.127480. Epub 2010 Apr 12.
Caspase activating and recruitment domain 8 (CARD8) has been implicated as a co-regulator of several pro-inflammatory and apoptotic signaling pathways. In the present study, we demonstrate a specific modulation of NOD2-induced signaling by CARD8 in intestinal epithelial cells. We show that CARD8 physically interacts with NOD2 and inhibits nodosome assembly and subsequent signaling upon muramyl-dipeptide stimulation. Furthermore, CARD8 inhibits the direct bactericidal effect of NOD2 against intracellular infection by Listeria monocytogenes. Thus, CARD8 represents a novel molecular switch involved in the endogenous regulation of NOD2-dependent inflammatory processes in epithelial cells.
Caspase activating and recruitment domain 8 (CARD8) 被认为是几种促炎和凋亡信号通路的共同调节因子。在本研究中,我们证明了 CARD8 在肠上皮细胞中对 NOD2 诱导的信号的特异性调节。我们发现 CARD8 与 NOD2 相互作用,并抑制 muramyl-dipeptide 刺激后的纳垢体组装和随后的信号转导。此外,CARD8 抑制了 NOD2 对李斯特菌属细胞内感染的直接杀菌作用。因此,CARD8 代表了一种新型的分子开关,参与了上皮细胞中 NOD2 依赖性炎症过程的内源性调节。