Antitumor activity of Porphyromonas gingivalis lipid A

用牙龈卟啉单胞菌脂质A(5Omcg/ml)体外孵育健康献血者外周血单个核细胞，观察其抗肿瘤活性和免疫调节作用。收集上清液，用ELISA法检测细胞因子IL-1γ、IL-1受体拮抗剂(IL-1ra)、IL-6、IL-8、GM-CSF、TNF-α、IFN-γ的活性。牙龈假单胞菌A类脂蛋白诱导的IL-1-α和肿瘤坏死因子-α的产生明显弱于细菌内毒素及其类脂A和沙门氏菌型类脂A诱导的IL-1ra的产生，而牙龈假单胞菌A类脂蛋白诱导的IL-1ra的产生高于螺旋杆菌及其类脂A诱导的IL-6、IL-8和GM-CSF的产生。在细胞杀伤实验中，牙龈假单胞菌的脂类A具有一定的杀瘤活性，但弱于其亲本LPS。牙龈假单胞菌及其脂类A的NK活性明显增强，与E线圈及其脂类A的NK活性基本相当。牙龈假单胞菌脂多糖对淋巴转移的抑制作用最强，提示其具有不同于肠杆菌脂类AS的免疫学活性，可诱导足够水平的抗肿瘤免疫。牙龈假单胞菌类脂A作为一种低毒的免疫调节剂具有临床应用的可能性，但在临床模型上有必要探索有效的给药方法。

We investigated the antitumor activity and immunomodulatory effects of P.gingivalis lipid A.Periphera blood mononuclear cells obtained from healthy donors were incubated with Porphyromonas gingivalis lipid A(5Omcg/ml) in vitro. The supernatants were harvested and measured the activities of cytokines such as IL-1gamma, IL-1 receptor antagonist (IL-1ra), IL-6, IL-8, GM-CSF.TNF-alpha and IFN-gamma by ELISA assay. P.gingivalis lipid A induced considerably weaker IL-1gamma and TNF-alpha production than did E.coil LPS and its lipid A and salmonella-type lipid A.ft gingivalis lipid A induced higher IL-1ra production than did F.coil LPS and its lipid A.P.gingivalis LPS and its lipid A induced high levels of IL-6, IL-8 and GM-CSF.IFN-gamma production was more strongly induced by Rgingivalis LPS than by the other test specimens.Cytostasis by splenic macrophages stimulated with ft gingivails LPS and its lipid A were enhanced significantly in a dose-dependent manner. In the cytolytic assay, ft gingivalis lipid A exhibited tumoricidal activities, but weaker than its parent LPS.NK activities of P.gingivalis LPS and its lipid A were enhanced and almost equivalent to those obtained with E coil LPS and its lipid A.P.gingivails lipid A were failed to inhibit regional lymph node metastasis of MM48 mammary carcinoma. P.gingivalis LPS most strongly inhibited the lymph nodes metastases.These results suggested that ft gingivails lipid A had different immunological activities from those of enterobacterial lipid As, and induced enough level of antitumor immunity. P.gingivalis lipid A has a possibility of clinical use as a low-toxic immunomodulator, but it is necessary to investigate the effective administration methods in clinical model.