• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Infection and immunity >Induction of Pro- and Anti-Inflammatory Cytokines by Borrelia burgdorferi Lipoproteins in Monocytes Is Mediated by CD14
【24h】

Induction of Pro- and Anti-Inflammatory Cytokines by Borrelia burgdorferi Lipoproteins in Monocytes Is Mediated by CD14

机译：伯氏疏螺旋体脂蛋白在单核细胞中的促炎和抗炎细胞因子的诱导是由CD14介导的。

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

We previously showed that heat-killed Borrelia burgdorferi spirochetes and lipidated outer surface protein A (L-OspA) stimulated the in vitro production of interleukin-10 (IL-10) in peripheral blood mononuclear cells (PBMC) from uninfected humans and rhesus monkeys (G. Giambartolomei et al., Infect. Immun. 66:2691–2697, 1998). Here we demonstrate that uninfected human peripheral blood monocytes, but not B or T cells, are the cells that transcribe the IL-10 cytokine gene in response to heat-killed B. burgdorferi. B. burgdorferi similarly induced an upregulation of the IL-1β and IL-6 cytokine genes in monocytes and the production of IL-10 and IL-6 in culture supernatants of the human monocytic cell line THP-1. Purified L-OspA (but not unlipidated OspA [U-OspA] or U-OspC) also stimulated the production of both cytokines in THP-1 cells in a dose-dependent fashion, suggesting that acylation of the OspA protein molecule is required for the production of both anti- and pro-inflammatory cytokines in naive monocytes. A lipohexapeptide that contained the tripalmitoyl-modified cysteine motif (Pam3Cys-Hex) of B. burgdorferi lipoproteins but with an arbitrary peptide sequence had the same effect. Monoclonal antibodies (MAbs) MY4 and 60bca, both of which bind to CD14 and are known to block lipopolysaccharide (LPS)-mediated cytokine production, were able to block L-OspA-mediated IL-10 and IL-6 cytokine production. In contrast, MAb 26ic, which also binds to CD14 but does not block LPS function, failed to inhibit L-OspA-mediated cytokine production. These data suggest that activation of monocytes and production of both anti- and pro-inflammatory cytokines induced by lipoproteins proceeds via the CD14 receptor. LPS binding protein was not required for OspA-induced cytokine production. Our results demonstrate that pro- and anti-inflammatory cytokines induced by B. burgdorferilipoproteins in PBMC are produced by monocytes and that lipoprotein and LPS signaling pathways share at least the initial signaling event that involves the CD14 receptor.
机译：我们先前显示，热灭活的 Borrelia burgdorferi 螺旋体和脂化的外表面蛋白A（L-OspA）刺激了外周血单核细胞（PBMC）中白细胞介素10（IL-10）的体外产生。来自未感染的人和恒河猴（G. Giambartolomei等，Infect。Immun。66：2691-2697，1998）。在这里，我们证明未受感染的人外周血单核细胞（而非B或T细胞）是响应热灭活的 B转录IL-10细胞因子基因的细胞。 burgdorferi 。 B。 burgdorferi 相似地诱导单核细胞THP-1培养上清中IL-1β和IL-6细胞因子基因的上调以及IL-10和IL-6的产生。纯化的L-OspA（但未脂化的OspA [U-OspA]或U-OspC）也以剂量依赖的方式刺激了THP-1细胞中两种细胞因子的产生，这表明OspA蛋白分子需要酰化。在幼稚单核细胞中产生抗炎和促炎性细胞因子。一种脂六肽，其中含有被 B修饰为半棕榈酰的半胱氨酸基序（Pam 3 Cys-Hex）。 burgdorferi脂蛋白但具有任意肽序列具有相同的效果。单克隆抗体（MAbs）MY4和60bca都与CD14结合，并且已知能够阻断脂多糖（LPS）介导的细胞因子的产生，它们能够阻断L-OspA介导的IL-10和IL-6的细胞因子的产生。相反，MAb 26ic也与CD14结合，但不阻断LPS功能，未能抑制L-OspA介导的细胞因子的产生。这些数据表明，脂蛋白诱导的单核细胞激活以及抗炎和促炎性细胞因子的产生均通过CD14受体进行。 OspA诱导的细胞因子生产不需要LPS结合蛋白。我们的结果证明了 B诱导的促炎和抗炎细胞因子。 PBMC中的burgdorferi脂蛋白由单核细胞产生，脂蛋白和LPS信号通路至少共享涉及CD14受体的初始信号事件。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号