Department of Environmental Toxicology, University of California, Davis, One Shields Avenue, Davis, CA 95616, USA.
Environ Health. 2012 Mar 28;11:17. doi: 10.1186/1476-069X-11-17.
The purpose of the present study was to investigate activation of inflammatory markers in human macrophages derived from the U937 cell line after exposure to particulate matter (PM) collected on dairy farms in California and to identify the most potent components of the PM.
PM from different dairies were collected and tested to induce an inflammatory response determined by the expression of various pro-inflammatory genes, such as Interleukin (IL)-8, in U937 derived macrophages. Gel shift and luciferase reporter assays were performed to examine the activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and Toll-like-receptor 4 (TLR4).
Macrophage exposure to PM derived from dairy farms significantly activated expression of pro-inflammatory genes, including IL-8, cyclooxygenase 2 and Tumor necrosis factor-alpha, which are hallmarks of inflammation. Acute phase proteins, such as serum amyloid A and IL-6, were also significantly upregulated in macrophages treated with PM from dairies. Coarse PM fractions demonstrated more pro-inflammatory activity on an equal-dose basis than fine PM. Urban PM collected from the same region as the dairy farms was associated with a lower concentration of endotoxin and produced significantly less IL-8 expression compared to PM collected on the dairy farms.
The present study provides evidence that the endotoxin components of the particles collected on dairies play a major role in mediating an inflammatory response through activation of TLR4 and NF-κB signaling.
本研究旨在探讨源自 U937 细胞系的人巨噬细胞在暴露于加利福尼亚州奶牛场采集的颗粒物后炎症标志物的激活情况，并确定 PM 中最有效的成分。
采集不同奶牛场的 PM 进行测试，以诱导 U937 衍生巨噬细胞中各种促炎基因（如白细胞介素 8 [IL-8]）的表达来确定炎症反应。凝胶迁移和荧光素酶报告基因检测用于检测核因子 κB（NF-κB）和 Toll 样受体 4（TLR4）的激活。
暴露于源自奶牛场的 PM 会显著激活促炎基因的表达，包括 IL-8、环氧化酶 2 和肿瘤坏死因子-α，这些都是炎症的标志。急性相蛋白，如血清淀粉样蛋白 A 和 IL-6，也在经 PM 处理的巨噬细胞中显著上调。与细颗粒物相比，粗颗粒物在相同剂量基础上表现出更强的促炎活性。从奶牛场所在同一地区采集的城市 PM 与内毒素浓度较低有关，与从奶牛场采集的 PM 相比，其 IL-8 表达明显减少。
本研究提供的证据表明，奶牛场采集的颗粒中的内毒素成分通过激活 TLR4 和 NF-κB 信号通路在介导炎症反应中起主要作用。
