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

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的能力中起着重要作用。一种诱导形式的NO合成酶（iNOS）在细胞因子和/或LPS刺激后负责巨噬细胞高输出生成NO。趋化因子是炎症反应的重要组成部分。体外实验表明，活的erinacei尾尾鱼可抑制ifn - γ和LPS刺激巨噬细胞iNOS和JE mRNA表达、单核细胞趋化蛋白-1的小鼠同源物表达以及亚硝酸盐的产生。尾鱼的排泄/分泌（ES）产物也能抑制诱导的iNOS和乙脑mRNA，并以剂量依赖性方式减少亚硝酸盐的产生。ES产物对巨噬细胞培养24 h后iNOS mRNA水平的抑制随刺激性质的不同而不同；IFN γ / lps诱导的iNOS mRNA水平受到的影响小于IFNgamma/IL-2或IFNgamma/TNFalpha诱导的iNOS mRNA水平。在测量亚硝酸盐产量时也得到了类似的结果。因此，mRNA水平似乎是ES产物的主要目标。甘油醛-3-磷酸脱氢酶基因的表达不受ES产物的影响。在没有巨噬细胞的情况下，NO供体药物s -亚硝基-乙酰-青霉胺或二乙胺二氧化二氮均不能在体外杀死破尾鱼，因此NO可能在宿主对破尾鱼的防御机制中并不重要。据推测，该抑制因子在ES产品中的主要生理作用可能是选择性下调lps诱导的基因表达，如趋化因子（JE和gro-alpha/KC），从而阻止白细胞的聚集，而不是特异性地阻止iNOS的表达。

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.