Sekine K, Ohta J, Onishi M, Tatsuki T, Shimokawa Y, Toida T, Kawashima T, Hashimoto Y
Bio-Chemical Research Laboratory, Morinaga Milk Industry Co., Ltd., Kanagawa.
Biol Pharm Bull. 1995 Jan;18(1):148-53. doi: 10.1248/bpb.18.148.
Intestinal Bifidobacterium species are thought to be beneficial in animal and human intestines. We studied the mechanisms of Bifidobacteria in antitumor activity using a cell wall preparation (WPG) of B. infantis (Cancer Res., 45, 1300, (1985)). WPG enhanced the in vitro antitumor activities of mouse peritoneal exudate cells elicited with proteose-peptone (P-PEC) and thioglycollate broth (TG-PEC), determined by cytostatic ([3H]thymidine uptake inhibition) and cytolytic ([3H]uridine release) assays. Tumor necrosis factor-alpha (TNF-alpha) and reactive nitrogen intermediates (RNI) play a role in such augmented cytotoxicity, because anti-TNF-alpha antibody almost completely blocked the increased cytolytic activity of P-PEC in the presence of WPG. Moreover, WPG induced RNI in the supernatant of TG-PEC in a dose-dependent manner. The mRNA expression of several cytokines (IL-1 beta, IL-6, IL-10, IFN-alpha and TNF-alpha) was induced in BALB/c mouse peritoneal cells 3 h after an intraperitoneal injection of WPG (3 h WPG-PEC). However, this expression disappeared from 24 h WPG-PEC, except for that of IFN-alpha. IFN-gamma was not induced. Kinetic studies of the tumor neutralizing activities of the WPG-PECs by means of the in vivo Winn assay revealed that the activity emerged at 1.5 h, became maximal at 3 h and disappeared at 24h. These results indicated that Bifidobacterial WPG is a Biological Response Modifier (BRM) with characteristics similar to those of other bacterial BRMs.
肠道双歧杆菌被认为对动物和人类肠道有益。我们使用婴儿双歧杆菌的细胞壁制剂（WPG）研究了双歧杆菌的抗肿瘤活性机制（《癌症研究》，45卷，1300页，（1985年））。WPG增强了用蛋白胨（P-PEC）和巯基乙酸盐肉汤（TG-PEC）诱导的小鼠腹腔渗出细胞的体外抗肿瘤活性，这通过细胞生长抑制（[3H]胸腺嘧啶核苷摄取抑制）和细胞溶解（[3H]尿苷释放）试验来测定。肿瘤坏死因子-α（TNF-α）和活性氮中间体（RNI）在这种增强的细胞毒性中起作用，因为抗TNF-α抗体几乎完全阻断了在WPG存在下P-PEC增加的细胞溶解活性。此外，WPG以剂量依赖性方式在TG-PEC的上清液中诱导RNI。在腹腔注射WPG（3小时WPG-PEC）后3小时，BALB/c小鼠腹腔细胞中几种细胞因子（IL-1β、IL-6、IL-10、IFN-α和TNF-α）的mRNA表达被诱导。然而，除了IFN-α外，这种表达在24小时WPG-PEC时消失。IFN-γ未被诱导。通过体内温氏试验对WPG-PEC的肿瘤中和活性进行动力学研究表明，该活性在1.5小时出现，在3小时达到最大值，并在24小时消失。这些结果表明双歧杆菌WPG是一种生物反应调节剂（BRM），其特征与其他细菌BRM相似。
