Department of Cellular and Molecular Biology, University of Texas Health Science Center at Tyler, USA.
Innate Immun. 2019 Feb;25(2):118-131. doi: 10.1177/1753425919827360.
Exposure to organic dust is a risk factor for the development of respiratory diseases. Surfactant proteins (SP) reduce alveolar surface tension and modulate innate immune responses to control lung inflammation. Therefore, changes in SP levels could contribute to the development of organic-dust-induced respiratory diseases. Because information on the effects of organic dust on SP levels is lacking, we studied the effects of dust from a poultry farm on SP expression. We found that dust extract reduced SP-A and SP-B mRNA and protein levels in H441 human lung epithelial cells by inhibiting their promoter activities, but did not have any effect on SP-D protein levels. Dust extract also reduced SP-A and SP-C levels in primary human alveolar epithelial cells. The inhibitory effects were not due to LPS or protease activities present in dust extract or mediated via oxidative stress, but were dependent on a heat-labile factor(s). Thyroid transcription factor-1, a key transcriptional activator of SP expression, was reduced in dust-extract-treated cells, indicating that its down-regulation mediates inhibition of SP levels. Our study implies that down-regulation of SP levels by organic dust could contribute to the development of lung inflammation and respiratory diseases in humans.
接触有机粉尘是引发呼吸道疾病的一个风险因素。表面活性剂蛋白（SP）可降低肺泡表面张力，并调节先天免疫反应以控制肺部炎症。因此，SP 水平的变化可能导致有机粉尘引起的呼吸道疾病的发生。由于缺乏有关有机粉尘对 SP 水平影响的信息，我们研究了来自家禽养殖场的粉尘对 SP 表达的影响。我们发现，粉尘提取物通过抑制其启动子活性，降低了 H441 人肺上皮细胞中 SP-A 和 SP-B 的 mRNA 和蛋白水平，但对 SP-D 蛋白水平没有影响。粉尘提取物还降低了原代人肺泡上皮细胞中 SP-A 和 SP-C 的水平。这种抑制作用不是由于粉尘提取物中存在 LPS 或蛋白酶活性，也不是通过氧化应激介导的，而是依赖于一种不耐热的因子。甲状腺转录因子-1是 SP 表达的关键转录激活因子，在粉尘提取物处理的细胞中减少，表明其下调介导了 SP 水平的抑制。我们的研究表明，有机粉尘对 SP 水平的下调可能导致人类肺部炎症和呼吸道疾病的发生。
