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Effects of parasites on the gene expression of nitric oxide synthase and cytokine in macrophages

寄生虫对巨噬细胞一氧化氮合酶和细胞因子基因表达的影响

基本信息

批准号：
09670259
负责人：
FUKUMOTO Soji
金额：
$ 1.98万
依托单位：
TOTTORI University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

项目摘要

Nitric oxide (NO) is important in the ability of mouse macrophages to kill infectious organisms including parasites. An inducible form of NO synthase (iNOS) is responsible for high output generation of NO by macrophages after stimulation with cytokines and/or LPS.Chemoattactant peptides termed chemokine are important components of the inflammatory response. Alive plerocercoids of Spirometra erinaceieuropaei suppressed the mRNA expression of iNOS and JE, murine homologue of monocyte chemotactic protein-1, and nitrite production of macrophages stimulated with IFN-gamma and LPS in vitro. Excretory/secretory (ES) products from plerocercoids also suppressed the induced iNOS and JE mRNA and reduce nitrite production in a dose dependent manner.Then we examined that the effects of preculture with plerocercoids on iNOS, chemokines (IP-l0, JE, KC) and TNF-alpha gene expression in peritoneal macrophages. The expression of mRNA was detected by northern hybridization and autoradiography, and mRNA expression levels were read by molecular image analyser using a phosphorescence screen. The gene expression of IP-l0 and JE in macrophages stimulated with LPS for 3 h was apparently suppressed by 5 plerocercoids in a preincubation-time dependent manner. TNF-alpha mRNA expression was also suppressed by preincubation with 5 plerocercoids. The suuprressive effect of iNOS gene expression in macrophages stimulated with IFN-gamma and LPS for 24 h was also observed by preincubation of ES products in a preincubation-time dependent manner. This inhibitory effects of ES products continued until 72 h after removal of ES products. Judging from these results, we suppose that ES products from plerocercoids might suppress the iNOS and chemokine gene expression of macrophages in vivo, and suppress the host defense mechanism.

一氧化氮（NO）在小鼠巨噬细胞杀死包括寄生虫在内的感染性生物体的能力中是重要的。一氧化氮合酶（iNOS）是巨噬细胞在细胞因子和/或脂多糖（LPS）刺激下产生大量NO的一种诱导型酶，趋化因子是炎症反应的重要组成部分。在体外，刺猬迭宫绦虫活的plerocercoids抑制了iNOS和JE的mRNA表达，单核细胞趋化蛋白-1的小鼠同源物，以及IFN-γ和LPS刺激的巨噬细胞亚硝酸盐的产生。本实验还观察了拟除虫菊酯预培养对腹腔巨噬细胞诱导型一氧化氮合酶（iNOS）、趋化因子（IP-10、JE、KC）和肿瘤坏死因子α（TNF-α）基因表达的影响。通过北方杂交和放射自显影检测mRNA的表达，并通过使用磷光屏的分子图像分析仪读取mRNA表达水平。LPS刺激巨噬细胞3 h后，5种拟尾蚴均能明显抑制巨噬细胞IP-10和JE基因表达，并呈时间依赖性。TNF-α mRNA的表达也被抑制预孵育与5 plerocercoids。用ES产物预孵育巨噬细胞24 h，可明显抑制IFN-γ和LPS刺激的巨噬细胞iNOS基因表达，并呈时间依赖性。ES产物的这种抑制作用持续到去除ES产物后72 h。由此推测，拟尾蚴的ES产物可能通过抑制体内巨噬细胞iNOS和趋化因子的基因表达，从而抑制宿主的防御机制。