Activation of human monocytic cells by Treponema pallidum and Borrelia burgdorferi lipoproteins and synthetic lipopeptides proceeds via a pathway distinct from that of lipopolysaccharide but involves the transcriptional activator NF-kappa B.

M V Norgard; L L Arndt; D R Akins; L L Curetty; D A Harrich; J D Radolf

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Activation of human monocytic cells by Treponema pallidum and Borrelia burgdorferi lipoproteins and synthetic lipopeptides proceeds via a pathway distinct from that of lipopolysaccharide but involves the transcriptional activator NF-kappa B.

机译：梅毒螺旋体和伯氏疏螺旋体脂蛋白和合成脂肽对人单核细胞的激活是通过不同于脂多糖的途径进行的，但涉及转录激活因子NF-κB。

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There is increasing evidence that lipoproteins of Treponema pallidum and Borrelia burgdorferi are key inflammatory mediators during syphilis and Lyme disease. A principal objective of the present study was to identify more precisely similarities and divergences among lipopolysaccharide (LPS)- and lipoprotein-lipopeptide-induced immune cell signaling events. Like LPS, purified native B. burgdorferi OspA and synthetic analogs of OspA, OspB, and two T. pallidum lipoproteins (Tpp47 and Tpp17) all induced NF-kappa B translocation in THP-1 human monocytoid cells. Acylation of OspA and the synthetic peptides was requisite for cell activation. Polymyxin B abrogated only the response to LPS. By using 70Z/3-derived pre-B-cell lines either lacking or expressing human CD14 (the LPS receptor), it was observed that expression of human CD14 imparted responsiveness to LPS but not to OspA or spirochetal lipopeptides (assessed by induction of NF-kappa B and expression of surface immunoglobulin M). Finally, the biological relevance of the observation that T. pallidum lipoproteins-lipopeptides induce both NF-kappa B and cytokine production in monocytes was supported by the ability of the synthetic analogs to promote human immunodeficiency virus replication in chronically infected U1 monocytoid cells; these observations also suggest a potential mechanism whereby a syphilitic chancre can serve as a cofactor for human immunodeficiency virus transmission. The combined data lend additional support to the proposal that spirochetal lipoproteins and LPS initiate monocyte activation via different cell surface events but that the signaling pathways ultimately converge to produce qualitatively similar cellular responses.

机译：越来越多的证据表明，梅毒螺旋体和伯氏疏螺旋体的脂蛋白是梅毒和莱姆病期间的关键炎症介质。本研究的主要目的是更准确地确定脂多糖（LPS）和脂蛋白-脂肽诱导的免疫细胞信号转导事件之间的相似性和差异。像LPS一样，纯化的天然伯氏疏螺旋体OspA和OspA，OspB的合成类似物，以及两种苍白螺旋体脂蛋白（Tpp47和Tpp17）都在THP-1人单核细胞中诱导NF-κB易位。 OspA和合成肽的酰化是细胞激活所必需的。多粘菌素B仅废除了对LPS的反应。通过使用缺乏或表达人CD14（LPS受体）的70Z / 3衍生的前B细胞系，可以观察到人CD14的表达赋予LPS反应性，但不赋予OspA或螺旋脂肽（通过诱导NF评估） -κB和表面免疫球蛋白M的表达）。最后，合成类似物在慢性感染的U1单核细胞中促进人类免疫缺陷病毒复制的能力支持了苍白球菌脂蛋白-脂肽在单核细胞中诱导NF-κB和细胞因子产生的观察结果的生物学意义。这些观察结果还表明梅毒性下cre可作为人免疫缺陷病毒传播的辅助因子的潜在机制。合并的数据为螺旋体脂蛋白和LPS通过不同的细胞表面事件启动单核细胞激活提供了额外的支持，但信号通路最终会收敛以产生质上相似的细胞反应。

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《Infection and immunity》 |1996年第9期|共8页
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M V Norgard; L L Arndt; D R Akins; L L Curetty; D A Harrich; J D Radolf;
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1. Treponema pallidum and Borrelia burgdorferi lipoproteins and synthetic lipopeptides activate monocytic cells via a CD14-dependent pathway distinct from that used by lipopolysaccharide. [J] . Sellati TJ, Bouis DA, Kitchens RL, The Journal of Immunology: Official Journal of the American Association of Immunologists . 1998,第11期

机译：梅毒螺旋体和伯氏疏螺旋体脂蛋白和合成脂肽通过CD14依赖性途径激活单核细胞，该途径不同于脂多糖。
2. Activation of human monocytic cells by Borrelia burgdorferi and Treponema pallidum is facilitated by CD14 and correlates with surface exposure of spirochetal lipoproteins. [J] . Sellati TJ, Bouis DA, Caimano MJ, The Journal of Immunology: Official Journal of the American Association of Immunologists . 1999,第4期

机译：CD14促进了伯氏疏螺旋体和苍白螺旋体对人单核细胞的激活，并与螺旋脂蛋白的表面暴露有关。
3. Transcriptional activation of the human TNF-alpha promoter by superantigen in human monocytic cells: role of NF-kappa B. [J] . Trede NS, Tsytsykova AV, Chatila T, The Journal of Immunology: Official Journal of the American Association of Immunologists . 1995,第2期

机译：超抗原在人单核细胞中转录激活人TNF-α启动子：NF-κB的作用。
4. Activation of matrix metalloproteinase -9 (MMP-9) by heregulin in human breast cancer cells involves multiple signaling pathways. [D] . Yao, Jun. 2000

机译：调蛋白在人乳腺癌细胞中对基质金属蛋白酶-9（MMP-9）的激活涉及多个信号通路。
5. Activation of human monocytic cells by Treponema pallidum and Borrelia burgdorferi lipoproteins and synthetic lipopeptides proceeds via a pathway distinct from that of lipopolysaccharide but involves the transcriptional activator NF-kappa B. [O] . M V Norgard, L L Arndt, D R Akins, 1996

机译：梅毒螺旋体和伯氏疏螺旋体脂蛋白和合成脂肽对人单核细胞的激活是通过不同于脂多糖的途径进行的但涉及转录激活因子NF-κB。
6. Activation of human monocytic cells by Treponema pallidum and Borrelia burgdorferi lipoproteins and synthetic lipopeptides proceeds via a pathway distinct from that of lipopolysaccharide but involves the transcriptional activator NF-kappa B [O] . M V Norgard, L L Arndt, D R Akins, 1996

机译：通过Treponema pallidum和Borrelia Burgdorferi脂蛋白和合成脂肽的活化通过不同于脂多糖的途径进行，但涉及转录活化剂NF-Kappa B.

Activation of human monocytic cells by Treponema pallidum and Borrelia burgdorferi lipoproteins and synthetic lipopeptides proceeds via a pathway distinct from that of lipopolysaccharide but involves the transcriptional activator NF-kappa B.

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