Chen Hsiu-Lin, Chong Inn-Wen, Lee Yi-Chen, Tsai Jong-Rung, Yuan Shyng-Shiou F, Wang Hui-Min, Liu Wei-Lun, Liu Po-Len
Department of Respiratory Therapy, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan ; Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan.
Department of Respiratory Therapy, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan ; Translational Research Center, Department of Medical Research, Department of Obstetrics and Gynecology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan ; Department of Internal Medicine, Department of Chest Surgery, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan.
Mediators Inflamm. 2014;2014:281984. doi: 10.1155/2014/281984. Epub 2014 Aug 12.
Acute lung injury (ALI) is associated with an inflammation-mediated process, and the transcription factor, Krüppel-like factor 5 (KLF5), might play a crucial role in inflammatory lung disease. In this study, we evaluated KLF5, reactive oxygen species (ROS), and inflammatory responses in a lipopolysaccharide- (LPS-) induced ALI model to elucidate the role of KLF5 in ALI. Our data indicated that LPS upregulates proinflammatory cytokine expression in human bronchial epithelial cells in a dose-dependent manner. We observed upregulated KLF5 protein expression in human bronchial epithelial cells exposed to LPS, with peak expression 1 h after LPS treatment, and subsequent upregulation of p65 protein expression and p65 phosphorylation at Ser276. These results indicate that KLF5 mediates proinflammatory cytokine expression by upregulating nuclear factor-kappaB (NF-κB) phosphorylation at p65 in response to LPS. LPS treatment also increased ROS production and simultaneously upregulated KLF5 expression and NF-κB translocation. N-acetylcysteine significantly reduced ROS levels and KLF5 and NF-κB translocation in nuclear extracts. Therefore, N-acetylcysteine pretreatment before LPS exposure reduces ROS, downregulates KLF5 expression, and subsequently reduces inflammatory responses by scavenging ROS. Overall, our study results indicate that KLF5 mediates proinflammatory cytokine expression through upregulation of NF-κB phosphorylation at p65 in LPS-induced ALI.
急性肺损伤（ALI）与炎症介导的过程相关，转录因子Krüppel样因子5（KLF5）可能在炎症性肺病中起关键作用。在本研究中，我们在脂多糖（LPS）诱导的ALI模型中评估了KLF5、活性氧（ROS）和炎症反应，以阐明KLF5在ALI中的作用。我们的数据表明，LPS以剂量依赖性方式上调人支气管上皮细胞中促炎细胞因子的表达。我们观察到暴露于LPS的人支气管上皮细胞中KLF5蛋白表达上调，LPS处理后1小时表达达到峰值，随后p65蛋白表达上调以及p65在Ser276处磷酸化。这些结果表明，KLF5通过上调p65处的核因子-κB（NF-κB）磷酸化来介导促炎细胞因子表达，以响应LPS。LPS处理还增加了ROS的产生，同时上调了KLF5表达和NF-κB易位。N-乙酰半胱氨酸显著降低了核提取物中的ROS水平以及KLF5和NF-κB易位。因此，在LPS暴露前用N-乙酰半胱氨酸预处理可降低ROS水平并下调KLF5表达，随后通过清除ROS减少炎症反应。总体而言，我们的研究结果表明，在LPS诱导的ALI中KLF5通过上调p65处的NF-κB磷酸化来介导促炎细胞因子表达。
