Organic dust induces inflammatory gene expression in lung epithelial cells via ROS-dependent STAT-3 activation.
Organic dust induces inflammatory gene expression in lung epithelial cells via ROS-dependent STAT-3 activation.
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有机粉尘通过 ROS 依赖性 STAT-3 激活诱导肺上皮细胞炎症基因表达。
DOI：
10.1152/ajplung.00448.2018
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Boggaram,Vijay
中科院分区：
文献类型：
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作者：
Natarajan,Kartiga;Meganathan,Velmurugan;Mitchell,Courtney;Boggaram,Vijay
暴露于农业和动物环境中的粉尘（称为有机粉尘）与呼吸道症状和呼吸道疾病的发展有关。炎症是与有机粉尘暴露相关的肺部病理学的关键特征，并且暴露于有机粉尘诱导几种免疫和炎症介质的表达。然而，有关转录因子和细胞和分子机制控制有机粉尘诱导的免疫和炎症介质的产生的信息是有限的。在这项研究中，我们已经确定了STAT-3作为一个重要的转录因子控制的诱导表达的免疫和炎症介质的家禽粉尘提取物在气道上皮细胞和小鼠肺，并划定了STAT-3激活的细胞途径。家禽粉尘提取物激活Beas 2B和正常人支气管上皮细胞和小鼠肺中的STAT-3磷酸化。STAT-3的化学抑制和siRNA敲低抑制了免疫和炎症介质表达的诱导。抗氧化剂抑制了家禽粉尘提取物诱导的STAT-3磷酸化的增加，表明氧化应激[活性氧（ROS）水平升高]对活化很重要。化学抑制和siRNA敲除实验表明，STAT-3激活依赖于非受体酪氨酸蛋白激酶2（TYK 2）和表皮生长因子受体（EGFR）酪氨酸激酶的激活。我们的研究表明，家禽粉尘提取物控制诱导免疫和炎症介质的表达，通过涉及氧化应激介导的STAT-3激活TYK 2和EGFR酪氨酸激酶的细胞途径。
Exposure to dust in agricultural and animal environments, known as organic dust, is associated with the development of respiratory symptoms and respiratory diseases. Inflammation is a key feature of lung pathologies associated with organic dust exposure, and exposure to organic dust induces the expression of several immune and inflammatory mediators. However, information on transcription factors and cellular and molecular mechanisms controlling the production of immune and inflammatory mediators induced by organic dust is limited. In this study, we have identified STAT-3 as an important transcription factor controlling the induction of expression of immune and inflammatory mediators by poultry dust extracts in airway epithelial cells and in mouse lungs and delineated the cellular pathway for STAT-3 activation. Poultry dust extract activated STAT-3 phosphorylation in Beas2B and normal human bronchial epithelial cells and in mouse lungs. Chemical inhibition and siRNA knockdown of STAT-3 suppressed induction of immune and inflammatory mediator expression. Antioxidants suppressed the increase of STAT-3 phosphorylation induced by poultry dust extract indicating that oxidative stress [elevated reactive oxygen species (ROS) levels] is important for the activation. Chemical inhibition and siRNA knockdown experiments demonstrated that STAT-3 activation is dependent on the activation of nonreceptor tyrosine-protein kinase 2 (TYK2) and epidermal growth factor receptor (EGFR) tyrosine kinases. Our studies show that poultry dust extract controls the induction of immune and inflammatory mediator expression via a cellular pathway involving oxidative stress-mediated STAT-3 activation by TYK2 and EGFR tyrosine kinases.