Institute for Health Science, Tokushima Bunri University, Nishihama, Yamashiro-cho, Tokushima-shi, 770-8514, Japan.
Anticancer Res. 2009 Nov;29(11):4871-7.
Intradermal or oral administration of lipopolysaccharide derived from Pantoea agglomerans (IP-PA1) has shown prophylactic and antitumor effects without serious side-effects. While it is known that tumor necrosis factor (TNF)-alpha produced by activated macrophages plays an important role in the expression mechanism following intradermal administration, details of the mechanism after oral administration remain unclear. In this study, the activation of innate immunity using fish as an animal model was investigated. In fish, the innate immunity system is dominant over acquired immunity.
Carp (Cyprinus carpio L) were fed IP-PA1 for 7 days. Total RNA was extracted from the head kidney (a major immune organ of teleost fish), and interleukin (IL) - 1beta, IL-6, IL-8, IL-10, IL-12, TNF-alpha and transforming forming growth factor (TGF)-beta mRNAs were quantified by one-step real-time PCR. Phagocytic and bactericidal activity of head kidney leukocytes were estimated using zymosan and Aeromonas hydrophila (a pathogenic bacteria), respectively. Serum lysozyme activity was assayed with Remazol brilliant Blue stained Micrococcus lysodeikticus.
Oral administration of IP-PA1 for 7 days augmented the quantity of mRNA expression of IL-1beta, IL-8, and TNF-alpha mRNA and reduced the expression level of IL-6 mRNA in the head kidney. Phagocytic and bactericidal activity of head kidney leukocytes were significantly enhanced. Moreover, serum lysozyme activities were significantly augmented.
The results suggest that oral administration of IP-PA1 induced activation of M1 type macrophages in the immune organ of fish, and this enhanced the function of pathogen elimination. Since the functions of macrophages are highly preserved in comparative immunology, there is a high probability that the preventative or curative effect on various diseases that have been observed in mammals is also related to the activation of macrophages to the M1 type.
经皮或口服聚生泛菌(Pantoea agglomerans)来源的脂多糖(IP-PA1)已显示出预防和抗肿瘤作用,且无严重副作用。虽然已知激活的巨噬细胞产生的肿瘤坏死因子(TNF)-α在皮内给药后的表达机制中发挥重要作用,但口服给药后的机制细节尚不清楚。本研究以鱼类为动物模型,研究了固有免疫的激活。在鱼类中,先天免疫系统优于获得性免疫系统。
用 IP-PA1 喂养鲤鱼(Cyprinus carpio L)7 天。从头肾(硬骨鱼的主要免疫器官)中提取总 RNA,并通过一步实时 PCR 定量测定白细胞介素(IL)-1β、IL-6、IL-8、IL-10、IL-12、TNF-α和转化生长因子(TGF)-β的 mRNA。分别使用酵母聚糖和嗜水气单胞菌(一种病原菌)估计头肾白细胞的吞噬和杀菌活性。使用 Remazol 亮蓝染色的溶壁微球菌测定血清溶菌酶活性。
口服 IP-PA1 7 天可增加头肾中 IL-1β、IL-8 和 TNF-α mRNA 的表达量,并降低 IL-6 mRNA 的表达水平。头肾白细胞的吞噬和杀菌活性显著增强。此外,血清溶菌酶活性显著增加。
结果表明,口服 IP-PA1 诱导了鱼类免疫器官中 M1 型巨噬细胞的激活,从而增强了病原体清除功能。由于比较免疫学中巨噬细胞的功能高度保守,因此在哺乳动物中观察到的各种疾病的预防或治疗效果很可能也与 M1 型巨噬细胞的激活有关。