HIF-1 expression is associated with CCL2 chemokine expression in airway inflammatory cells: implications in allergic airway inflammation.
HIF-1 expression is associated with CCL2 chemokine expression in airway inflammatory cells: implications in allergic airway inflammation.
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DOI：
10.1186/1465-9921-13-60
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发表时间：
2012-07-23
影响因子：
5.8
通讯作者：
Huerta-Yepez S
中科院分区：
文献类型：
--
作者：
Baay-Guzman GJ;Bebenek IG;Zeidler M;Hernandez-Pando R;Vega MI;Garcia-Zepeda EA;Antonio-Andres G;Bonavida B;Riedl M;Kleerup E;Tashkin DP;Hankinson O;Huerta-Yepez S
哮喘患者过敏性气道炎症的发病机制复杂，以细胞浸润和多种细胞因子和趋化因子的活性为特征。转录因子缺氧诱导因子-1（HIF-1）和趋化因子CCL 2已被证明在过敏性气道炎症中起关键作用。这两个因素之间的相互关系尚不清楚。我们推测HIF-1和CCL 2的表达可能存在相关性，CCL 2的表达可能受HIF-1的调控。几条线的证据来支持这一假设。测定用上调HIF的3，4-二羟基苯甲酸乙酯（EDHB）处理野生型OVA（卵清蛋白）致敏/激发小鼠对CCL 2表达的影响。检测HIF-1β有条件敲除的小鼠在气管内暴露于卵清蛋白后在肺中产生过敏性炎症反应和CCL 2表达的能力。在哮喘患者激发后的支气管内活检和支气管液中也检测了HIF-1α和CCL 2水平的相关性。我们发现，在卵清蛋白（OVA）诱导的小鼠过敏反应过程中，HIF-1α和CCL 2均上调。在用上调HIF-1α的药理学试剂3，4-二羟基苯甲酸乙酯（EDHB）处理后，HIF-1α和CCL 2的水平显著增加。相反，与野生型小鼠中的水平相比，在用OVA致敏后条件性敲除ARNT（HIF-1β）的小鼠的肺中，HIF-1α和CCL 2的表达水平降低。在哮喘患者中，HIF-1α和CCL 2的水平在用过敏原激发后增加。这些数据表明，CCL 2的表达部分受到肺部HIF-1的调节。这些发现还表明，CCL 2和HIF-1都涉及过敏性气道炎症的发病机制。
The pathogenesis of allergic airway inflammation in asthmatic patients is complex and characterized by cellular infiltrates and activity of many cytokines and chemokines. Both the transcription factor hypoxia inducible factor-1 (HIF-1) and chemokine CCL2 have been shown to play pivotal roles in allergic airway inflammation. The interrelationship between these two factors is not known. We hypothesized that the expression of HIF-1 and CCL2 may be correlated and that the expression of CCL2 may be under the regulation of HIF-1. Several lines of evidence are presented to support this hypothesis. The effects of treating wild-type OVA (ovalbumin)-sensitized/challenged mice with ethyl-3,4-dihydroxybenzoate (EDHB), which upregulate HIF, on CCL2 expression, were determined. Mice conditionally knocked out for HIF-1β was examined for their ability to mount an allergic inflammatory response and CCL2 expression in the lung after intratracheal exposure to ovalbumin. The association of HIF-1α and CCL2 levels was also measured in endobronchial biopsies and bronchial fluid of asthma patients after challenge. We show that both HIF-1α and CCL2 were upregulated during an OVA (ovalbumin)-induced allergic response in mice. The levels of HIF-1α and CCL2 were significantly increased following treatment with a pharmacological agent which upregulates HIF-1α, ethyl-3,4-dihydroxybenzoate (EDHB). In contrast, the expression levels of HIF-1α and CCL2 were decreased in the lungs of mice that have been conditionally knocked out for ARNT (HIF-1β) following sensitization with OVA when compared to levels in wild type mice. In asthma patients, the levels of HIF-1α and CCL2 increased after challenge with the allergen. These data suggest that CCL2 expression is regulated, in part, by HIF-1 in the lung. These findings also demonstrate that both CCL2 and HIF-1 are implicated in the pathogenesis of allergic airway inflammation.
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影响因子：
14.2
作者：
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通讯作者：
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影响因子：
9.6
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