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

寄生虫对巨噬细胞一氧化氮合酶和趋化因子基因表达的影响

基本信息

批准号：
06670257
负责人：
FUKUMOTO Soji
金额：
$ 1.41万
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：
1994
资助国家：
日本
起止时间：
1994 至 1996
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-06670257/
关键词：
parasite macrophage nitric oxide synthase chemokine gene expression northern blot Spirometra erimacei 擬充尾虫 TNFα プレロセルコイド一酸化窒素合成酸素 Northern Blotting 遺伝子発現抑制インターフェロン-γ

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 erinacei 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. The suppression of iNOS mRNA levels in macrophages cultured for 24 h with ES products varied with the nature of the stimuli ; IFN gamma/LPS-induced iNOS mRNA levels were effected less than were iNOS mRNA levels induced by IFNgamma/IL-2 or IFNgamma/TNFalpha. Similar findings were obtained when nitrite production was measured. Thus mRNA levels appear to be the primary target of ES products. The expression of the glyceraldehyde-3-phosphate dehydrogenase gene was unaffected by the ES products. The NO donor drugs, S-nitroso-acetyl-penicillamine or diethylamine dinitric oxide, were unable to kill plerocercoids in vitro in the absence of macrophages, therefore NO might not be important in the host's defense mechanism to plerocercoids. It is supposed that a main physiological role of this inhibitory factor in ES products might be selectively down regulation of LPS-inducible gene expressions such as chemokines (JE and gro-alpha/KC) thereby preventing the accumlation of leukocytes, but not preventing the iNOS expression specifically.

一氧化氮（NO）在小鼠巨噬细胞杀死包括寄生虫在内的传染性生物的能力中很重要。 NO合酶（INOS）的一种可诱导形式是用细胞因子和/或LPS刺激后，巨噬细胞的高输出生成NO的高输出生成。EmoAttactactant肽肽称为趋化因子是炎症反应的重要组成部分。螺旋体的生命plerocerocoid抑制了iNOS和JE的mRNA表达，单核细胞趋化蛋白1的鼠同源物以及亚二硝酸盐在体外用IFN-gamma和LPS刺激的巨噬细胞产生的巨噬细胞。来自Pleroceroids的排泄/分泌（ES）产物也抑制了诱导的iNOS和JE mRNA，并以剂量依赖性方式降低亚硝酸盐的产生。与ES产物培养的巨噬细胞中iNOS mRNA水平的抑制作用随刺激的性质而变化。 IFNγ/LPS诱导的iNOS mRNA水平的影响小于IFNGAMMA/IL-2或IFNGAMMA/TNFALPHA诱导的INOS mRNA水平。测量亚硝酸盐产生时，获得了类似的发现。因此，mRNA水平似乎是ES产物的主要目标。 ES产物不影响甘油醛-3-磷酸脱氢酶基因的表达。 NO供体药物，S-亚硝基 - 乙酰基 - 苯胺或二乙胺二氧化物氧化物，在没有巨噬细胞的情况下无法在体外杀死Pleroceroids，因此，在宿主的防御机制中，没有可能并不重要。据认为，该抑制因子在ES产物中的主要生理作用可能被选择性地调节LPS诱导基因表达（例如趋化因子（JE和GRO-ALPHA/KC）），从而防止白细胞的累积，但不能特别防止INOS表达。