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

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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.