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.

粘虫排泄/分泌产物能抑制脂多糖或干扰素-γ刺激的巨噬细胞的IP-10基因表达，但不能抑制IRF-1基因的表达。脂多糖刺激的巨噬细胞中的IP-10基因将被干扰素β通过MyD88非依赖途径诱导，ES产物不仅抑制干扰素-β基因的表达，而且还抑制IP-10基因的表达，Northern印迹分析或RTPCR证实了这一点。ES产物在内毒素刺激3h后抑制巨噬细胞STAT-1Tyr701的磷酸化，但不抑制干扰素-γ刺激的STAT-1Tyr701的磷酸化。凝胶漂移实验结果表明，在加入ES产物的情况下，干扰素-γ或干扰素-β刺激的巨噬细胞中STAT-1或ISGF3的核转位和DNA结合活性没有改变。然后，我们检测了ES产物对含有-243启动子或IP-10增强子区域的荧光素酶载体的巨噬细胞荧光素酶活性的影响。ES产物可抑制脂多糖和br-干扰素-γ刺激的巨噬细胞荧光素酶活性。这些结果表明，ES产物抑制IP-10基因表达的机制不是基于抑制转录因子STAT-1和NF-κB的结合活性，而是源于IP-10启动子的构象。ES产物也抑制了诱导型一氧化氮合酶和亚硝酸盐的产生，但增强了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）。