Department of Geriatrics, Wuhan Fourth Hospital, Affiliated Puai Hospital of Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China.
Department of Emergency Medicine, Wuhan Fourth Hospital, Affiliated Puai Hospital of Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China.
PLoS One. 2023 Feb 15;18(2):e0277719. doi: 10.1371/journal.pone.0277719. eCollection 2023.
This study was aimed to investigate the role of interleukin-1β (IL-1β) in cigarette smoke extract (CSE)-induced apoptosis in vascular smooth muscle cells and the underlying mechanism in a rat derived cell line.
Rat thoracic aortic smooth muscle cells (A7r5) were divided into six groups including control, CSE (model), CSE+ overexpression empty vector (OvExp-EV), CSE+IL-1β knockdown (KD), and CSE+ IL-1β knockdown empty vector (KD-EV). The mRNA expression levels of IL-1β and pregnancy-associated plasma protein A (PAPP-A) were detected by quantitative polymerase chain reaction (qPCR). The apoptosis of A7r5 cells was detected by flow cytometry. The expression levels of inflammatory mediators (TNFα, IL-6 and IL-8) and apoptotic proteins (Bax and Bcl-2) were determined by western blot.
CSE induced significant apoptosis in vascular smooth muscle cells (P < 0.01) and elevated the mRNA levels of IL-1β and PAPP-A (P < 0.01). CSE administration increased protein expression of Bax, TNF-α, IL-6, and IL-8, with significantly reduced Bcl-2 expression (P < 0.01). IL-1β knockdown significantly decreased cell apoptosis via regulating the expression of these proteins (P < 0.05 or P < 0.01).
IL-1β is involved in CSE-induced PAPP-A expression and apoptosis in vascular smooth muscle cells, which might be considered as a target for preventing of cardiovascular diseases caused by cigarette smoking.
本研究旨在探讨白细胞介素-1β（IL-1β）在香烟烟雾提取物（CSE）诱导血管平滑肌细胞凋亡中的作用及其在大鼠衍生细胞系中的潜在机制。
将大鼠胸主动脉平滑肌细胞（A7r5）分为六组，包括对照组、CSE（模型组）、CSE+过表达空载体（OvExp-EV）组、CSE+IL-1β 敲低（KD）组和 CSE+IL-1β 敲低空载体（KD-EV）组。采用实时定量聚合酶链反应（qPCR）检测 IL-1β 和妊娠相关血浆蛋白 A（PAPP-A）的 mRNA 表达水平。采用流式细胞术检测 A7r5 细胞的凋亡情况。采用 Western blot 检测炎症介质（TNFα、IL-6 和 IL-8）和凋亡蛋白（Bax 和 Bcl-2）的表达水平。
CSE 显著诱导血管平滑肌细胞凋亡（P < 0.01），并上调 IL-1β 和 PAPP-A 的 mRNA 水平（P < 0.01）。CSE 处理增加了 Bax、TNF-α、IL-6 和 IL-8 的蛋白表达，Bcl-2 的表达明显降低（P < 0.01）。IL-1β 敲低通过调节这些蛋白的表达显著降低细胞凋亡（P < 0.05 或 P < 0.01）。
IL-1β 参与 CSE 诱导的血管平滑肌细胞 PAPP-A 表达和凋亡，可作为预防吸烟引起的心血管疾病的靶点。
