Research on a parasite factor suppressing the gene expression of TNF-α and chemokines in macrophages

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Excretory/secretory (ES) products from Spirometra erinaceieuropaei plerocercoids suppressed the IP-10 gene expression, but not IRF-1, in macrophages stimulated with LPS or IFN-γ. IP-10 gene in LPS-stimulated macrophages will be induced by IFN-β through the MyD88 independent pathway, and ES products suppressed not only IFN-β gene expression but also IP-10, which was clarified by Northern blot analysis or RT-PCR. ES products suppressed the phosphorylation of STAT-1 Tyr701 in macrophages 3 h after the stimulation with LPS, but did not suppress the phosphorylation in the case of IFN-γ stimulation. The data of gel shift assay showed that the nuclear translocation and DNA binding activity of STAT-1 or ISGF3 did not change in macrophages stimulated with IFN-γ or IFN-β by the addition of ES products. Then, we examined the effects of ES products on the luciferase activities of macrophages transfected with luciferase vector containing -243 promoter or enhancer region of IP-10, which is the minimum response region. ES products suppressed the luciferase activities of macrophages stimulated with LPS and br IFN-γ. These data suggest that the suppressive mechanisms of IP-10 gene expression by ES products did not based on the inhibition of DNA binding activity of transcription factors such as STAT-1 and NF-κB, and originated from the conformation in IP-10 promoter. ES products also suppressed inducible nitric oxide synthase and the nitrite production, but ES products increased the CIITA and MHCII gene expression in the IFN-γ stimulated macrophages.