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摘要
鼻疽是类鼻疽的病原体和代表潜在的生物恐怖威胁。在这项研究中,使用人巨噬细胞的模型B杆菌感染的转录反应进行了调查全基因组微阵列。基因表达谱感染的THP-1人单核细胞白血病细胞用或不用圆斑(DRRDbTx)或头孢他啶(抗生素对照)治疗之间进行比较。感染的和经处理的细胞显示的各种炎性基因,如白介素-1(IL-1),IL-6,肿瘤坏死因子-α(TNF-α),环氧合酶(COX-2),血管内皮生长差动上调的微阵列分析因子(VEGF),趋化因子CXC基序配体4(CXCL4),转录因子p65的(NF-kB的);和参与免疫和应激反应,细胞周期,和脂质代谢的几个基因。此外,以下的DRR-DbTx治疗感染的细胞,有增强的tolllike受体2(TLR-2)参与识别和急性炎症反应引发介导的信号传导途径的表达。重要的是,我们观察到高度的炎性细胞因子基因的反应是在感染细胞24小时后暴露在与DRR DbTx或头孢他啶类似。此外,还有增加的细胞死亡蛋白酶激活,可以促进宿主组织损伤。总之,在巨噬细胞的B杆菌感染的转录反应突出广泛的在24小时后感染激活先天性免疫机制。这些数据提供深入了解以下DRR-DbTx治疗感染B杆菌的人巨噬细胞的转录动力学。
关键词: 类鼻疽杆菌,基因表达,促炎因子,人类巨噬细胞,毒液蛋白
Current Molecular Medicine
Title:Gene Microarray Analyses of Daboia russelli russelli Daboiatoxin Treatment of THP-1 Human Macrophages Infected with Burkholderia pseudomallei.
Volume: 15 Issue: 10
Author(s): R. Perumal Samy, J. Manikandan, A. Pachiappan, E.E. Ooi, L.T. Aw, B.G. Stiles, O.L. Franco, M. Kandasamy, K.M. Mathi, G. Rane, K.S. Siveen, C. Arunachalam, M.E. Zayed, S.A. Alharbi and A.P. Kumar, G. Sethi, L.H.K. Lim and V.T. Chow
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关键词: 类鼻疽杆菌,基因表达,促炎因子,人类巨噬细胞,毒液蛋白
摘要: Burkholderia pseudomallei is the causative agent of melioidosis and represents a potential bioterrorism threat. In this study, the transcriptomic responses of B. pseudomallei infection of a human macrophage cell model were investigated using whole-genome microarrays. Gene expression profiles were compared between infected THP-1 human monocytic leukemia cells with or without treatment with Daboia russelli russelli daboiatoxin (DRRDbTx) or ceftazidime (antibiotic control). Microarray analyses of infected and treated cells revealed differential upregulation of various inflammatory genes such as interleukin-1 (IL-1), IL-6, tumor necrosis factor-alpha (TNF-α), cyclooxygenase (COX-2), vascular endothelial growth factor (VEGF), chemokine C-X-C motif ligand 4 (CXCL4), transcription factor p65 (NF-kB); and several genes involved in immune and stress responses, cell cycle, and lipid metabolism. Moreover, following DRR-DbTx treatment of infected cells, there was enhanced expression of the tolllike receptor 2 (TLR-2) mediated signaling pathway involved in recognition and initiation of acute inflammatory responses. Importantly, we observed that highly inflammatory cytokine gene responses were similar in infected cells exposed to DRR-DbTx or ceftazidime after 24 h. Additionally, there were increased transcripts associated with cell death by caspase activation that can promote host tissue injury. In summary, the transcriptional responses during B. pseudomallei infection of macrophages highlight a broad range of innate immune mechanisms that are activated within 24 h post-infection. These data provide insights into the transcriptomic kinetics following DRR-DbTx treatment of human macrophages infected with B. pseudomallei.
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R. Perumal Samy, J. Manikandan, A. Pachiappan, E.E. Ooi, L.T. Aw, B.G. Stiles, O.L. Franco , M. Kandasamy, K.M. Mathi, G. Rane, K.S. Siveen, C. Arunachalam, M.E. Zayed, S.A. Alharbi and A.P. Kumar, G. Sethi, L.H.K. Lim and V.T. Chow , Gene Microarray Analyses of Daboia russelli russelli Daboiatoxin Treatment of THP-1 Human Macrophages Infected with Burkholderia pseudomallei., Current Molecular Medicine 2015; 15 (10) . https://dx.doi.org/10.2174/1566524016666151123114123
DOI https://dx.doi.org/10.2174/1566524016666151123114123 |
Print ISSN 1566-5240 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5666 |
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