Regulation of CYP1A1 and Inflammatory Cytokine by NCOA7 Isoform 4 in Response to Dioxin Induced Airway Inflammation
Regulation of CYP1A1 and Inflammatory Cytokine by NCOA7 Isoform 4 in Response to Dioxin Induced Airway Inflammation
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DOI：
10.4046/trd.2015.78.2.99
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发表时间：
2015-04-01
影响因子：
2.9
通讯作者：
Kim, Woo Jin
中科院分区：
文献类型：
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作者：
Cho, Sung-Hwan;Park, Shin Young;Kim, Woo Jin
背景：芳烃受体（Aryl hydrocarbon receptor, AhR）是一种依赖配体的转录因子，可与多种合成和天然化合物结合。AhR参与急性和慢性呼吸道疾病期间炎症反应的调节。我们研究了核受体共激活因子7 （NCOA7）是否可以调节2,3,7,8-四氯二苯并-对二恶英（TCDD）处理的人支气管上皮细胞AhR靶基因和炎症因子的转录水平。本研究基于我们前期关于NCOA7在正常与慢性阻塞性肺疾病肺组织中表达差异的研究。方法：转染pCMV-NCOA7亚型4后，在无血清条件下培养的BEAS-2B和A549细胞分别用TCDD （0.15 nM和6.5 nM）处理24小时。实时定量聚合酶链反应检测细胞色素P4501A1 （CYP1A1）、IL-6、IL-8的表达水平。结果：TCDD在BEAS-2B和A549细胞系中均能强烈诱导CYP1A1和炎症因子的转录活性。NCOA7亚型4在BEAS-2B和A549细胞系之间反向调节CYP1A1和炎症细胞因子的转录活性。结论：NCOA7在正常和异常生理条件下可作为TCDD-AhR信号通路的调节因子，发挥双重作用。
Background: Aryl hydrocarbon receptor (AhR), a ligand-dependent transcription factor, binds to a wide variety of synthetic and naturally occurring compounds. AhR is involved in the regulation of inflammatory response during acute and chronic respiratory diseases. We investigated whether nuclear receptor coactivator 7 (NCOA7) could regulate transcriptional levels of AhR target genes and inflammatory cytokines in 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)treated human bronchial epithelial cells. This study was based on our previous study that NCOA7 was differentially expressed between normal and chronic obstructive pulmonary disease lung tissues.Methods: BEAS-2B and A549 cells grown under serum-free conditions were treated with or without TCDD (0.15 nM and 6.5 nM) for 24 hours after transfection of pCMV-NCOA7 isoform 4. Expression levels of cytochrome P4501A1 (CYP1A1), IL-6, and IL-8 were measured by quantitative real-time polymerase chain reaction.Results: The transcriptional activities of CYP1A1 and inflammatory cytokines were strongly induced by TCDD treatment in both BEAS-2B and A549 cell lines. The NCOA7 isoform 4 oppositely regulated the transcriptional activities of CYP1A1 and inflammatory cytokines between BEAS-2B and A549 cell lines.Conclusion: Our results suggest that NCOA7 could act as a regulator in the TCDD-AhR signaling pathway with dual roles in normal and abnormal physiological conditions.