Analysis of global gene expression changes in human bronchial epithelial cells exposed to spores of the allergenic fungus, Alternaria alternata.

Analysis of global gene expression changes in human bronchial epithelial cells exposed to spores of the allergenic fungus, Alternaria alternata.
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DOI:
10.3389/fmicb.2013.00196
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发表时间:
2013
影响因子:
5.2
通讯作者:
Lawrence CB
Lawrence CB
中科院分区:
生物学2区
文献类型:
--
作者:
Babiceanu MC;Howard BA;Rumore AC;Kita H;Lawrence CB

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长期以来,暴露于空气中普遍存在的真菌(如链格孢菌)并对其敏感,与慢性过敏性气道疾病的发生、发作和恶化有关。本研究是第一个调查的全球变化过程中培养的人支气管上皮细胞和活的链格孢孢子的宿主基因表达。在体外实验中,将人支气管上皮细胞(BEAS-2B)暴露于孢子或单独的培养基24小时。从每次处理的三个生物学重复中收集RNA,并使用Affytechnic Human Genome U133 Plus 2.0 Arrays用于评估基因表达模式的变化。在用链格孢属孢子处理的细胞中,与对照相比,发现代表460个个体基因的613个探针组差异表达(p ≤ 0.05)。在这组460个具有统计学意义的差异表达基因中,发现397个基因上调,63个基因下调。在这397个上调基因中,发现156个基因上调≥2倍。有趣的是,63个下调基因中没有发现差异表达≤-2倍。差异表达的基因在统计分析后鉴定,随后用于途径和网络评估。有趣的是,许多细胞因子和趋化因子免疫应答基因上调,特别强调干扰素诱导基因。参与细胞死亡、视黄酸信号传导和TLR 3反应途径的基因也显著上调。许多差异上调的基因已在其他系统中显示与先天免疫、炎症和/或过敏性气道疾病相关。本研究为进一步研究链格孢菌在过敏性气道疾病中激活的特异性基因和先天免疫系统通路提供了大量信息。
Exposure and sensitivity to ubiquitous airborne fungi such as Alternaria alternata have long been implicated in the development, onset, and exacerbation of chronic allergic airway disorders. This present study is the first to investigate global changes in host gene expression during the interaction of cultured human bronchial epithelial cells and live Alternaria spores. In in vitro experiments human bronchial epithelial cells (BEAS-2B) were exposed to spores or media alone for 24 h. RNA was collected from three biological replicates per treatment and was used to assess changes in gene expression patterns using Affymetrix Human Genome U133 Plus 2.0 Arrays. In cells treated with Alternaria spores compared to controls, 613 probe sets representing 460 individual genes were found differentially expressed (p ≤ 0.05). In this set of 460 statistically significant, differentially expressed genes, 397 genes were found to be up-regulated and 63 were down-regulated. Of these 397 up-regulated genes, 156 genes were found to be up-regulated ≥2 fold. Interestingly, none of the 63 down-regulated genes were found differentially expressed at ≤−2 fold. Differentially expressed genes were identified following statistical analysis and subsequently used for pathway and network evaluation. Interestingly, many cytokine and chemokine immune response genes were up-regulated with a particular emphasis on interferon-inducible genes. Genes involved in cell death, retinoic acid signaling, and TLR3 response pathways were also significantly up-regulated. Many of the differentially up-regulated genes have been shown in other systems to be associated with innate immunity, inflammation and/or allergic airway diseases. This study now provides substantial information for further investigating specific genes and innate immune system pathways activated by Alternaria in the context of allergic airway diseases.
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