Peripheral blood IRF1 expression as a marker for glucocorticoid sensitivity
Peripheral blood IRF1 expression as a marker for glucocorticoid sensitivity
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DOI：
10.1097/fpc.0000000000000116
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发表时间：
2015-03-01
影响因子：
2.6
通讯作者：
Huang, Rong S.
中科院分区：
文献类型：
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作者：
Chapin, William J.;Lenkala, Divya;Huang, Rong S.
目的尽管糖皮质激素（GCs）被广泛使用，但仍有相当一部分哮喘患者表现为糖皮质激素不敏感。这可能由多种机制介导，包括基因组学。最近的研究表明，测量基因表达的变化可能比单独的基线基因表达提供更多关于GC不敏感的预测信息，并且外周血中的表达变化可能反映了气道中的表达变化。方法利用基因表达综合（GEO）数据进行硅发现，评估GC对多种组织类型基因表达的影响。随后，在细胞系和来源于人气道和血液的原代细胞中检测了表达水平受GC影响的候选基因。结果通过基因表达综合分析，我们在气道平滑肌细胞、正常人支气管上皮细胞（NHBE）和淋巴母细胞样细胞系（LCLs）中鉴定出干扰素调节因子1 (IRF1)，其表达受GC处理的影响。在两种培养的气道上皮细胞系和原代NHBE细胞中证实了GC暴露后IRF1的显著下调(P
Objective Despite of the common usage of glucocorticoids (GCs), a significant portion of asthma patients exhibit GC insensitivity. This could be mediated by diverse mechanisms, including genomics. Recent work has suggested that measuring changes in gene expression may provide more predictive information about GC insensitivity than baseline gene expression alone, and that expression changes in peripheral blood may be reflective of those in the airway.Methods We performed in silico discovery using gene expression omnibus (GEO) data that evaluated GC effect on gene expression in multiple tissue types. Subsequently, candidate genes whose expression levels are affected by GC were examined in cell lines and in primary cells derived from human airway and blood.Results Through gene expression omnibus analysis, we identified interferon regulator factor 1 (IRF1), whose expression is affected by GC treatment in airway smooth muscle cells, normal human bronchial epithelial (NHBE) cells, and lymphoblastoid cell lines (LCLs). Significant IRF1 downregulation post GC exposure was confirmed in two cultured airway epithelial cell lines and primary NHBE cells (P