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

抑制巨噬细胞TNF-α和趋化因子基因表达的寄生虫因子的研究

• 批准号: 13670246
• 负责人: FUKUMOTO Soji
• 金额: $ 2.3万
• 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: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670246/
• 关键词: Spirometra erinaceieuropaei; Excretory; secretory products; macrophage; IP-10; chemokine; gene expression; LPS; IFN-γ; INF-γ; TNF-α; NF-кB; MAPK

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.

在用LPS或IFN-γ刺激的巨噬细胞中，来自螺旋体的Erinaceieuropaei pleropocoids的排泄/分泌（ES）产物抑制了IP-10基因表达，而不是IRF-1。 IFN-β通过MYD88独立途径诱导LPS刺激的巨噬细胞中的IP-10基因，ES产物不仅抑制了IFN-β基因表达，还抑制了IP-10，通过Northern Blot分析或RT-PCR阐明了IP-10。 ES产物在用LPS刺激后3小时抑制了巨噬细胞中Stat-1 Tyr701的磷酸化，但在IFN-γ刺激的情况下没有抑制磷酸化。凝胶移位测定的数据表明，通过添加ES产物，STAT-1或ISGF3的核转运和DNA结合活性在被IFN-γ或IFN-β刺激的巨噬细胞中没有变化。然后，我们检查了ES产物对含有-243启动子或IP -10增强子区域（最小响应区域）的荧光素酶矢量翻译的巨噬细胞荧光素酶活性的影响。 ES产物抑制了LPS和BR IFN-γ刺激的巨噬细胞的荧光素酶活性。这些数据表明，ES产物对IP-10基因表达的抑制机制不是基于转录因子（例如Stat-1和NF-κB）的DNA结合活性的抑制，而是源自IP-10启动子中的会议。 ES产物还抑制了可诱导的一氧化氮合酶和亚硝酸盐的产生，但是ES产物增加了IFN-γ刺激的巨噬细胞中CIITA和MHCII基因的表达。

项目成果

P.Dirgahayu, S.Fukumoto, S.Tademoto, K.Hirai: "Regulation of TNF-α, IL-1β and ICAM-1 gene expression in THP-1 monocytes stimulated with Plasmodium falciparum-cultured medium by excretory/secretory products from Spirometra erinacei-europaei plerocercoids."

P.Dirgahayu、S.Fukumoto、S.Tademoto、K.Hirai：“用恶性疟原虫培养液刺激的 THP-1 单核细胞中的排泄/分泌产物对 TNF-α、IL-1β 和 ICAM-1 基因表达的调节Spirometra erinacei-europae plerocercoids。”

P.Dirgahayu, S.Fukumoto, S.Tademoto, K.Hirai: "Regulation of TNF-α, IL-1β and ICAM-1 gene expression in THP-1 monocytes stimulated with Plasmodium falciparum-cultured medium by excretory/secretory products from Spirometra erinaceieuropaei plerocercoids."Y

P.Dirgahayu、S.Fukumoto、S.Tademoto、K.Hirai：“用恶性疟原虫培养液刺激的 THP-1 单核细胞中的排泄/分泌产物对 TNF-α、IL-1β 和 ICAM-1 基因表达的调节erinaceieuropaei plerocercoids."Y

福本宗嗣, 三浦憲豊, Dirgahayu Paramasari, 平井和光: "マンソン裂頭条虫によるマクロファージの抑制作用"臨床免疫. 39・2. 141-148 (2003)

Soji Fukumoto、Noritoyo Miura、Dirgahayu Paramasari、Kazumitsu Hirai：“曼索尼绦虫对巨噬细胞的抑制作用”临床免疫学 39・2（2003）。

P.Dirgahayu, S.Fukumoto, S.Tademoto, K.Kina, K.Hirai: "Excretory/secretory products from plerocercoids of Spirometra erinaceieuropaei suppress IL-1β gene expression in murine macrophages."International Journal for Parasitology. (In press). (2004)

P.Dirgahayu、S.Fukumoto、S.Tademoto、K.Kina、K.Hirai：“来自 Spirometra erinaceieuropaei 的 plerocercoids 的排泄/分泌产物抑制小鼠巨噬细胞中的 IL-1β 基因表达。”国际寄生虫学杂志（正在出版）。 (2004)

福本 宗嗣: "マンソン裂頭条虫によるマクロファージの抑制作用"臨床免疫. 39・2. 141-148 (2003)

Munetsugu Fukumoto：“曼索尼绦虫对巨噬细胞的抑制作用”临床免疫学39・2（2003）。