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Divergence of canonical danger signals: the genome-level expression patterns of human mononuclear cells subjected to heat shock or lipopolysaccharide.
BMC Immunology ( IF 2.9 ) Pub Date : 2008-05-30 , DOI: 10.1186/1471-2172-9-24
Hector R Wong 1 , Kelli Odoms , Bhuvaneswari Sakthivel
Affiliation  

BACKGROUND Peripheral blood mononuclear cells (PBMC) serve a sentinel role allowing the host to efficiently sense and adapt to the presence of danger signals. Herein we have directly compared the genome-level expression patterns (microarray) of a human PBMC model (THP-1 cells) subjected to one of two canonical danger signals, heat shock or lipopolysaccharide (LPS). RESULTS AND DISCUSSION Based on sequential expression and statistical filters, and in comparison to control cells, we found that 3,988 genes were differentially regulated in THP-1 cells subjected to LPS stress, and 2,921 genes were differentially regulated in THP-1 cells subjected to heat shock stress. Venn analyses demonstrated that the majority of differentially regulated genes (> or = 70%) were uniquely expressed in response to one of the two danger signals. Functional analyses demonstrated that the two danger signals induced expression or repression of genes corresponding to unique pathways, molecular functions, biological processes, and gene networks. In contrast, there were 184 genes that were commonly upregulated by both stress signals, and 430 genes that were commonly downregulated by both stress signals. Interestingly, the 184 commonly upregulated genes corresponded to a gene network broadly related to inflammation, and more specifically to chemokine signaling. CONCLUSION These data demonstrate that the mononuclear cell responses to the canonical stress signals, heat shock and LPS, are highly divergent. However, there is a heretofore unrecognized common pattern of gene network expression corresponding to chemokine-related biology. The data also serve as a reference database for investigators in the field of stress signaling.

中文翻译:

典型危险信号的分歧:人类单核细胞在热休克或脂多糖作用下的基因组水平表达模式。

背景外周血单核细胞(PBMC)起到哨兵的作用,允许宿主有效地感知和适应危险信号的存在。在此,我们直接比较了受两种典型危险信号之一、热休克或脂多糖 (LPS) 影响的人类 PBMC 模型(THP-1 细胞)的基因组水平表达模式(微阵列)。结果与讨论 基于序列表达和统计过滤器,并与对照细胞相比,我们发现在受到 LPS 胁迫的 THP-1 细胞中,有 3,988 个基因被差异调控,而在受热的 THP-1 细胞中,有 2,921 个基因被差异调控。冲击应力。维恩分析表明,大多数差异调节基因(> 或 = 70%)在响应两个危险信号之一时被独特表达。功能分析表明,这两种危险信号诱导了与独特途径、分子功能、生物过程和基因网络相对应的基因的表达或抑制。相比之下,有 184 个基因通常被两种胁迫信号上调,430 个基因通常被两种胁迫信号下调。有趣的是,这 184 个普遍上调的基因对应于与炎症广泛相关的基因网络,更具体地说,与趋化因子信号传导相关。结论 这些数据表明,单核细胞对经典应激信号、热休克和 LPS 的反应是高度不同的。然而,与趋化因子相关生物学相对应的基因网络表达有一种迄今为止未被认识的共同模式。
更新日期:2019-11-01
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