Department of Rheumatology and Immunology, The First Affiliated Hospital of Shantou University Medical College, Shantou, China.
Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Shantou University Medical College, Shantou, China.
Arch Med Res. 2023 Jun;54(4):277-286. doi: 10.1016/j.arcmed.2023.03.005. Epub 2023 Mar 27.
Chronic obstructive pulmonary disease and other respiratory inflammatory diseases are often associated with cigarette smoke exposure. However, the underlying molecular mechanism remains unclear.
This study aimed to investigate the role of sphingosine-1-phosphate receptor 2 (S1PR2) in cigarette smoke extract (CSE)-induced inflammation and pyroptosis in human bronchial epithelial (HBE) cells.
CSE was administered to HBE cells and inflammation and pyroptosis were assessed. The mRNA levels of S1PR2, NLRP3, IL-1β, and IL-18 in HBE cells were detected by quantitative RT-PCR. Secreted protein levels of IL-1β and IL-18 in the culture supernatants were detected using enzyme-linked immunosorbent assay. Western blotting was used to measure the levels of S1PR2 and pyroptosis-related proteins (NLRP3, ASC, caspase-1, GSDMD, IL-1β, and IL-18).
Our study revealed an upregulated expression of S1PR2, NLRP3, ASC, caspase-1, GSDMD, IL-1β, and regulated IL-18 in HBE cells after CSE exposure. Genetic blockage of S1PR2 could reverse the increased expression of these proteins related to CSE-induced pyroptosis. Conversely, S1PR2 overexpression increased CSE-induced pyroptosis by upregulating the expression of NLRP3, ASC, caspase-1, GSDMD, IL-1β, and IL-18 in HBE cells.
Our results revealed that a novel S1PR2 signaling pathway may be involved in the pathogenesis of CSE-induced inflammation and pyroptosis in HBE cells. Thus, S1PR2 inhibitors could be an effective treatment for cigarette smoke-induced airway inflammation and injury.
慢性阻塞性肺疾病和其他呼吸道炎症性疾病通常与吸烟有关。然而，其潜在的分子机制尚不清楚。
本研究旨在探讨鞘氨醇-1-磷酸受体 2（S1PR2）在香烟烟雾提取物（CSE）诱导的人支气管上皮（HBE）细胞炎症和细胞焦亡中的作用。
用 CSE 处理 HBE 细胞，评估炎症和细胞焦亡。用实时定量 RT-PCR 检测 HBE 细胞中 S1PR2、NLRP3、IL-1β 和 IL-18 的 mRNA 水平。用酶联免疫吸附试验检测培养上清液中 IL-1β 和 IL-18 的分泌蛋白水平。用 Western blot 检测 S1PR2 和细胞焦亡相关蛋白（NLRP3、ASC、caspase-1、GSDMD、IL-1β 和 IL-18）的水平。
本研究显示，CSE 暴露后 HBE 细胞中 S1PR2、NLRP3、ASC、caspase-1、GSDMD、IL-1β 和调节的 IL-18 表达上调。S1PR2 基因阻断可逆转 CSE 诱导的细胞焦亡相关蛋白表达增加。相反，S1PR2 过表达通过上调 HBE 细胞中 NLRP3、ASC、caspase-1、GSDMD、IL-1β 和 IL-18 的表达，增加 CSE 诱导的细胞焦亡。
本研究结果表明，S1PR2 信号通路可能参与了 CSE 诱导的 HBE 细胞炎症和焦亡的发病机制。因此，S1PR2 抑制剂可能是一种治疗香烟烟雾诱导的气道炎症和损伤的有效方法。
