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Interleukin-8 Is Differentially Expressed by Human-Derived Monocytic Cell Line U937 Infected with Mycobacterium tuberculosis H37Rv and Mycobacterium marinum

机译:白细胞介素8由感染结核分枝杆菌H37Rv和海洋分枝杆菌的人源单核细胞系U937差异表达。

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摘要

Although Mycobacterium marinum is closely related to Mycobacterium tuberculosis H37Rv genomically, the clinical outcome in humans is quite different for M. marinum and M. tuberculosis infections. We investigated possible factors in the host macrophages for determining differential pathological responses to M. tuberculosis and M. marinum using an in vitro model of mycobacterial infection. Using suppression-subtractive hybridization, we identified 12 differentially expressed genes in the human monocytic cell line U937 infected with M. tuberculosis and M. marinum. Of those genes, the most frequently recovered transcript encoded interleukin-8 (IL-8). Northern hybridization revealed that IL-8 mRNA was highly upregulated in M. tuberculosis-infected U937 cells compared with M. marinum-infected cells. In addition, enzyme-linked immunosorbent assay showed that IL-8 protein secretion was significantly elevated in M. tuberculosis-infected U937 cells, human primary monocytes, and monocyte-derived macrophages compared with that in M. marinum-infected cells. The depressed IL-8 expression was unique in M. marinum-infected cells compared with cells infected with other strains of mycobacteria, including M. tuberculosis H37Ra, Mycobacterium bovis BCG, or Mycobacterium smegmatis. When the expression of NF-κB was assessed in mycobacterium-infected U937 cells, IκBα proteins were significantly degraded in M. tuberculosis-infected cells compared with M. marinum-infected cells. Collectively, these results suggest that differential IL-8 expression in human macrophages infected with M. tuberculosis and M. marinum may be critically associated with distinct host responses in tuberculosis. Additionally, our data indicate that differential signal transduction pathways may underlie the distinct patterns of IL-8 secretion in cells infected by the two mycobacteria.
机译:尽管海马分枝杆菌在基因组学上与结核分枝杆菌H37Rv密切相关,但人类对于海分枝杆菌和结核分枝杆菌感染的临床结局却大不相同。我们使用分枝杆菌感染的体外模型调查了宿主巨噬细胞中可能的因素,以确定对结核分枝杆菌和海藻分枝杆菌的不同病理反应。使用抑制消减杂交,我们在感染结核分枝杆菌和海藻分枝杆菌的人单核细胞系U937中鉴定了12个差异表达的基因。在那些基因中,最常回收的转录本编码白介素8(IL-8)。 Northern杂交显示与结核分枝杆菌感染的细胞相比,结核分枝杆菌感染的U937细胞中IL-8 mRNA高度上调。此外,酶联免疫吸附试验表明,与感染海藻支原体的细胞相比,结核分枝杆菌感染的U937细胞,人原代单核细胞和单核细胞衍生的巨噬细胞中IL-8蛋白的分泌显着增加。与感染了其他分枝杆菌菌株(包括结核分枝杆菌H37Ra,牛分枝杆菌BCG或耻垢分枝杆菌)的细胞相比,在感染了海藻支原体的细胞中,IL-8表达的下降是独特的。当评估分枝杆菌感染的U937细胞中NF-κB的表达时,与结核分枝杆菌感染的细胞相比,结核分枝杆菌感染的细胞中IκBα蛋白显着降解。总体而言,这些结果表明,在感染了结核分枝杆菌和海藻分枝杆菌的人类巨噬细胞中,IL-8表达的差异可能与结核病中不同的宿主反应密切相关。此外,我们的数据表明,在两个分枝杆菌感染的细胞中,不同的信号转导途径可能是IL-8分泌模式的不同。

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