Cytokine responses to CpG DNA in human leukocytes
Cytokine responses to CpG DNA in human leukocytes
复制标题
DOI：
10.1111/j.1365-3083.2006.01779.x
复制
发表时间：
2006-07-01
影响因子：
3.7
通讯作者：
Aasen, A. O.
中科院分区：
文献类型：
--
作者：
gren, J.;Thiemermann, C.;Aasen, A. O.
先前的研究表明，含有未甲基化胞嘧啶-磷酸-鸟苷 (CpG) 基序的细菌 DNA 在引发全身炎症中发挥着重要作用。这是基于 CpG-DNA 与脂多糖 (LPS) 协同作用的能力，触发小鼠单核细胞中肿瘤坏死因子 α (TNF α) 的产生，并增强啮齿动物中的 LPS 毒性。在这项研究中，我们研究了 CpG-DNA 在人类白细胞中触发和调节细胞因子反应的能力。将人类血液测定以及单核细胞和中性粒细胞的分离培养物暴露于合成寡脱氧核苷酸 (ODN) CpG ODN 单独或与 peptidogly (2006) 和 GpC ODN (2006-GC)、can 或 LPS 组合。分离血浆或上清液，并通过 ELISA 分析 TNF α、白介素-1 β (IL-1 β)、IL-6 和 IL-8。 在血液中，2006（但不是 2006-GC）诱导 TNF α 的释放（p < 0.05）以及可能的 IL-1 β 和 IL-6 的释放。 IL-8 以不依赖 CpG 的方式诱导。当与肽聚糖共同给药时，两种 ODN 都会增强细胞因子的释放，但并不总是依赖于 CpG。当与 LPS 共同给药时，仅 IL-8 值增强，而 IL-6 在早期时间点受到抑制。在单核细胞和中性粒细胞培养物中，未观察到 CpG 依赖性细胞因子释放诱导。然而，两种 ODN 均抑制 LPS 诱导的 IL-6。总之，CpG DNA 触发 TNF α 释放和增强 LPS 诱导的该细胞因子释放的能力在人全血中得到证实，但在贴壁人单核细胞中并未得到证实。 ODN 对人类白细胞细胞因子释放的大多数影响与 CpG 无关。
Previous studies have implicated a role of bacterial DNA, containing unmethylated cytosine-phosphate-guanosine (CpG) motifs, in the initiation of systemic inflammation. This is based on the ability of CpG-DNA to act in synergy with lipopolysaccharide (LPS) to trigger tumor necrosis factor alpha (TNF alpha) production in murine monocytes and to enhance LPS toxicity in rodents. In this study we investigated the capacity of CpG-DNA to trigger and modulate cytokine responses in human leukocytes.A human blood assay, as well as isolated cultures of monocytes and neutrophils, was exposed to the synthetic oligodeoxynucleotides (ODNs) CpG ODN alone or in combination with peptidogly(2006) and GpC ODN (2006-GC), can or LPS. Plasma or supernatants were isolated and analyzed for TNF alpha, interleukin-1 beta (IL-l beta), IL-6 and IL-8 by ELISA.In the blood, 2006 (but not 2006-GC) induced the release of TNF alpha (p < 0.05) and possibly IL-1 beta and IL-6. IL-8 was induced in a CpG-independent manner. When co-administered with peptidoglycan, both ODNs enhanced the release of cytokines, but not consistently CpG dependent. When co-administered with LPS, only IL-8 values were enhanced, whereas IL-6 was suppressed at early time points. In monocyte and neutrophil cultures, CpG dependent induction of cytokine release was not observed. However, both ODNs inhibited LPS-induced IL-6.In conclusion, the capacity of CpG DNA to trigger the release of TNF alpha and to enhance LPS-induced release of this cytokine is confirmed in human whole blood, but not in adherent human monocytes. Most effects of the ODNs on cytokine release in human leukocytes were CpG independent.