Department of Pediatrics, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Niao-sung Hsiang, Kaohsiung Hsien 833, Taiwan.
Mediators Inflamm. 2009;2009:103890. doi: 10.1155/2009/103890. Epub 2010 Feb 24.
Following Salmonella invasion, intestinal epithelial cells release a distinct array of proinflammatory cytokines. Interleukin (IL)-6 produced by enterocytes may have anti-inflammatory and cell-protective effects, and may counteract some of the injurious effects of sepsis and endotoxemia. Recent studies in a variety of rodent models of experimental colitis by using PJ-34, a potent poly (ADP-ribose) polymerase-1 (PARP-1) inhibitor, support the concept that the marked beneficial effect of PJ-34 can be exploited to treat human inflammatory diseases. The present study was to investigate the effect of PJ-34 on Salmonella-induced enterocyte IL-6 production and its mechanisms. We found that PJ-34 enhanced Salmonella-induced IL-6 production in Caco-2 cells, either secreted protein or mRNA expression. PJ-34 treatment enhanced the activity of NF-kappaB in Salmonella-infected Caco-2 cells. Besides, the involvement of PJ-34 in up-regulating IL-6 production in S. typhimurium-infected Caco-2 cells might be also through the ERK but not p38 MAPK, JNK or PI3K/Akt pathways, as demonstrated by Western blot of phosphorylated ERK, p38, JNK and Akt proteins. It suggests that PJ-34 may exert its protective effect on intestinal epithelial cells against invasive Salmonella infection by up-regulating IL-6 production through ERK and NF-kappaB but not P38 MAPK, JNK or PI3K/Akt signal pathways.
沙门氏菌入侵后，肠上皮细胞会释放出一系列特定的促炎细胞因子。肠细胞产生的白细胞介素（IL）-6 可能具有抗炎和细胞保护作用，并可能抵消败血症和内毒素血症的一些损伤作用。最近在各种实验性结肠炎的啮齿动物模型中使用强效多聚（ADP-核糖）聚合酶-1（PARP-1）抑制剂 PJ-34 的研究支持了这样一种观点，即 PJ-34 的显著有益作用可以被利用来治疗人类炎症性疾病。本研究旨在探讨 PJ-34 对沙门氏菌诱导的肠细胞 IL-6 产生的影响及其机制。我们发现，PJ-34 增强了 Caco-2 细胞中沙门氏菌诱导的 IL-6 产生，无论是分泌蛋白还是 mRNA 表达。PJ-34 处理增强了沙门氏菌感染的 Caco-2 细胞中 NF-κB 的活性。此外，PJ-34 上调鼠伤寒沙门氏菌感染的 Caco-2 细胞中 IL-6 产生的作用也可能通过 ERK 而不是 p38 MAPK、JNK 或 PI3K/Akt 途径，如磷酸化 ERK、p38、JNK 和 Akt 蛋白的 Western blot 所示。这表明 PJ-34 可能通过 ERK 和 NF-κB 而不是 P38 MAPK、JNK 或 PI3K/Akt 信号通路上调 IL-6 产生，从而对肠上皮细胞发挥保护作用，抵抗侵袭性沙门氏菌感染。
