Department of Immunology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan; Department of Immunology, Norman Bethune College of Medicine, Jilin University, Changchun, China.
Department of Immunology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan.
Toxicol Lett. 2014 Sep 2;229(2):384-92. doi: 10.1016/j.toxlet.2014.06.021. Epub 2014 Jul 5.
Acrolein, a compound found in cigarette smoke, is a major risk factor for respiratory diseases. Previous research determined that both acrolein and cigarette smoke produced reactive oxygen species (ROS). As many types of pulmonary injuries are associated with inflammation, this study sought to ascertain the extent to which exposure to acrolein advanced inflammatory state in the lungs. Our results showed that intranasal exposure of mice to acrolein increased CD11c(+)F4/80(high) macrophages in the lungs and increased ROS formation via induction of NF-κB signaling. Treatment with acrolein activated macrophages and led to their increased production of ROS and expression of several key pro-inflammatory cytokines. In in vitro studies, acrolein treatment of bone marrow-derived GM-CSF-dependent immature macrophages (GM-IMs), activated the cells and led to their increased production of ROS and expression of several key pro-inflammatory cytokines. Acrolein treatment of macrophages induced apoptosis of lung epithelial cells. Inclusion of an inhibitor of ROS formation markedly decreased acrolein-mediated macrophage activation and reduced the extent of epithelial cell death. These results indicate that acrolein can cause lung damage, in great part by mediating the increased release of pro-inflammatory cytokines/factors by macrophages.
丙烯醛，一种存在于香烟烟雾中的化合物，是呼吸道疾病的主要危险因素。之前的研究确定丙烯醛和香烟烟雾都会产生活性氧物质（ROS）。由于许多类型的肺部损伤都与炎症有关，因此这项研究旨在确定接触丙烯醛会在多大程度上加剧肺部的炎症状态。我们的结果表明，通过诱导 NF-κB 信号通路，将小鼠鼻腔暴露于丙烯醛会增加肺部的 CD11c（+）F4/80（高）巨噬细胞，并增加 ROS 的形成。丙烯醛处理会激活巨噬细胞，并导致其 ROS 的产生和几种关键促炎细胞因子的表达增加。在体外研究中，丙烯醛处理骨髓来源的 GM-CSF 依赖性未成熟巨噬细胞（GM-IMs）会激活细胞，并导致其 ROS 的产生和几种关键促炎细胞因子的表达增加。丙烯醛处理诱导肺上皮细胞凋亡。ROS 形成抑制剂的加入显著减少了丙烯醛介导的巨噬细胞激活，并降低了上皮细胞死亡的程度。这些结果表明，丙烯醛可通过介导巨噬细胞释放更多的促炎细胞因子/因子，导致肺部损伤。
