Toll-like receptor 5 (TLR5) and nucleotide-binding oligomerization domain 2 (Nod2) are two important pattern recognition receptors involved in innate immunity to invading pathogens. Flagellin, recognized by TLR5, is Salmonella's dominant pro-inflammatory determinant in intestinal epithelial cells (IECs). Nod2 has played a pivotal role in protecting against intestinal bacterial infection. Therefore the aim of the study is to investigate regulation of Salmonella flagellin-induced interleukin (IL)-8 (IL-8) in IECs by Nod2 agonist, muramyl dipeptide (MDP). We found that MDP by itself induced only a weak IL-8 secretion in Caco-2 cells. However, it did show synergistic enhancement on flagellin-induced IL-8 production in Caco-2 cells, possibly caused by flagellin-mediated enhanced Nod2 recruitment into cell membrane. By Western blot and siRNA, we showed ERK and NF-κB, Nod2 and Rip2 were involved in the synergistic effect of MDP. These findings suggested that the cooperation of TLR5 and Nod2 in IECs regulates inflammatory response to Salmonella infection.

中文翻译：

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鼠酰胺基二肽对沙门氏菌鞭毛蛋白诱导的肠上皮细胞白介素8的调节。

Toll样受体5（TLR5）和核苷酸结合寡聚域2（Nod2）是两个重要的模式识别受体，涉及对病原体的先天免疫。由TLR5识别的鞭毛蛋白是沙门氏菌在肠上皮细胞（IEC）中的主要促炎性决定因素。Nod2在预防肠道细菌感染方面发挥了关键作用。因此，本研究的目的是研究Nod2激动剂，戊二酰二肽（MDP）对沙门氏菌鞭毛蛋白诱导的白介素（IL）-8（IL-8）在IEC中的调节作用。我们发现MDP本身仅在Caco-2细胞中诱导弱的IL-8分泌。但是，它确实显示了鞭毛蛋白诱导的Caco-2细胞中IL-8产生协同增强，这可能是由于鞭毛蛋白介导的Nod2募集进入细胞膜而引起的。通过Western blot和siRNA，我们显示ERK和NF-κB，Nod2和Rip2参与了MDP的协同作用。这些发现表明IEC中TLR5和Nod2的合作调节了沙门氏菌感染的炎症反应。