Department of Pulmonary and Critical Care Medicine, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, China.
Department of Pulmonary Disease, Jinan Traditional Chinese Medicine Hospital, Jinan 250012, China.
Life Sci. 2021 Mar 15;269:119090. doi: 10.1016/j.lfs.2021.119090. Epub 2021 Jan 16.
Pyroptosis and inflammation are involved in the development of chronic obstructive pulmonary disease (COPD). However, the cigarette smoke-mediated mechanism of COPD remains unclear. In this study, we aimed to investigate the role of nucleotide-binding domain-like receptor protein-3 (NLRP3) inflammasome-mediated pyroptosis in the death of human bronchial epithelial (HBE) cells after cigarette smoke extract (CSE) exposure.
The protein level of NLRP3 in lung tissue was measured after cigarette smoke exposure in vivo. In vitro, HBE cells were treated with CSE. Subsequently, the activity of caspase-1, lactate dehydrogenase (LDH) release, release of interleukin (IL)-1β and NLRP3 expression levels were measured. The involvement of reactive oxygen species (ROS) was also explored.
After exposure to CSE, increased release of LDH, the transcriptional and translational upregulation of NLRP3, the caspase-1 activity levels, and enhanced IL-1β and IL-18 release were observed in 16HBE cells. In addition, NLRP3 was required to activate the caspase-1. Our results suggested that pre-stimulated of 16HBE with a caspase-1 inhibitor, or using NLRP3 siRNA to silence NLRP3 expression, also caused the decrease of IL-1β release and pyroptosis.
CSE induced inflammation and contributed to pyroptosis through the ROS/NLRP3/caspase-1 pathway in 16HBE cells. The NLRP3 inflammasome participates in CSE-induced HBE cell damage and pyroptosis, which could provide new insights into COPD.
细胞焦亡和炎症参与了慢性阻塞性肺疾病（COPD）的发展。然而，香烟烟雾介导的 COPD 发病机制仍不清楚。在本研究中，我们旨在研究核苷酸结合寡聚结构域样受体蛋白 3（NLRP3）炎性小体介导线粒体细胞凋亡在香烟烟雾提取物（CSE）暴露后人类支气管上皮（HBE）细胞死亡中的作用。
体内香烟烟雾暴露后测量肺组织中 NLRP3 的蛋白水平。体外，用 CSE 处理 HBE 细胞。随后，测量 caspase-1 活性、乳酸脱氢酶（LDH）释放、白细胞介素（IL）-1β释放和 NLRP3 表达水平。还探讨了活性氧（ROS）的参与情况。
暴露于 CSE 后，16HBE 细胞中 LDH 释放增加，NLRP3 的转录和翻译上调，caspase-1 活性水平升高，IL-1β和 IL-18 释放增强。此外，NLRP3 需要激活 caspase-1。我们的结果表明，预先用 caspase-1 抑制剂刺激 16HBE，或使用 NLRP3 siRNA 沉默 NLRP3 表达，也会导致 IL-1β 释放和细胞焦亡减少。
CSE 通过 ROS/NLRP3/caspase-1 通路诱导 16HBE 细胞炎症，并导致细胞焦亡。NLRP3 炎性小体参与 CSE 诱导的 HBE 细胞损伤和细胞焦亡，这为 COPD 提供了新的见解。
