School of Veterinary Medicine, Department of Pathology, Microbiology, and Immunology, University of California, Davis, CA 95616, United States.
Toxicol In Vitro. 2011 Dec;25(8):1895-905. doi: 10.1016/j.tiv.2011.06.001. Epub 2011 Jun 15.
Environmental particulate matter (PM) exposure has been correlated with pathogenesis of acute airway inflammatory disease such as asthma and COPD. PM size and concentration have been studied extensively, but the additional effects of particulate components such as biological material, transition metals, and polycyclic aromatic hydrocarbons could also impact initial disease pathogenesis. In this study, we compared urban ambient particulate matter (APM) collected from Fresno, California with wildfire (WF) particulate matter collected from Escalon, California on early transcriptional responses in human bronchial epithelial cells (HBE). Global gene expression profiling of APM treated HBE activated genes related to xenobiotic metabolism (CYP 1B1), endogenous ROS generation and response genes (DUOX1, SOD2, PTGS2) and pro-inflammatory responses associated with asthma or COPD such as IL-1α, IL-1β, IL-8, and CCL20. WF PM treatments also induced a pro-inflammatory gene response, but elicited a more robust xenobiotic metabolism and oxidative stress response. Inhibitor studies targeting endotoxin, ROS, and trace metals, found endotoxin inhibition had modest selective inhibition of inflammation while inhibition of hydrogen peroxide and transition metals had broad effects suggesting additional interactions with xenobiotic metabolism pathways. APM induced a greater inflammatory response while WF PM had more marked metabolism and ROS related responses.
环境颗粒物(PM)暴露与急性气道炎症性疾病(如哮喘和 COPD)的发病机制有关。已经广泛研究了 PM 的大小和浓度,但颗粒物成分(如生物物质、过渡金属和多环芳烃)的其他影响也可能影响初始疾病发病机制。在这项研究中,我们比较了来自加利福尼亚州弗雷斯诺的城市环境颗粒物(APM)和来自加利福尼亚州埃斯卡隆的野火颗粒物(WFPM)对人支气管上皮细胞(HBE)的早期转录反应的影响。APM 处理的 HBE 的全基因表达谱激活了与外源物代谢(CYP1B1)、内源性 ROS 生成和反应基因(DUOX1、SOD2、PTGS2)相关的基因,以及与哮喘或 COPD 相关的促炎反应,如 IL-1α、IL-1β、IL-8 和 CCL20。WFPM 处理也诱导了促炎基因反应,但引起了更强的外源物代谢和氧化应激反应。针对内毒素、ROS 和痕量金属的抑制剂研究发现,内毒素抑制剂对炎症有适度的选择性抑制作用,而抑制过氧化氢和过渡金属则有广泛的影响,表明与外源物代谢途径有额外的相互作用。APM 诱导了更强的炎症反应,而 WFPM 则有更明显的代谢和 ROS 相关反应。