Department of Medical Technology, School of Life and Environmental Science, Azabu University, Kanagawa, Japan;
Research Institute for Healthy Living, Niigata University of Pharmacy and Applied Life Sciences, Niigata, Japan.
Anticancer Res. 2022 Aug;42(8):4049-4054. doi: 10.21873/anticanres.15901.
BACKGROUND/AIM: Vascular endothelial cells play an important role in regulating immune responses and in keeping the balance between blood coagulation and fibrinolysis. Inflammatory cytokines produced by activated macrophages and vascular endothelial cells excessively activate vascular endothelial cells, leading to an imbalance in the expression of blood coagulation- and fibrinolysis-related factors. The dysfunction of vascular endothelial cells can lead to development of various diseases. In a previous study the increased expression of inflammatory cytokines in adipocytes was shown to be suppressed by the culture medium of macrophages activated by low-dose lipopolysaccharide (LPS). Suppressing inflammatory cytokine gene expression of low-dose LPS-activated macrophages may allow for the regulation of the dysfunction in vascular endothelial cells.
Human monocytes THP-1 cells were differentiated into macrophages with phorbol 12-myristate 13-acetate (PMA) and were activated with LPS. The culture medium of the LPS-activated THP-1 was added to human aortic endothelial cells (HAoEC). After five days, the expression of inflammatory cytokine genes interleukin (IL)1B, IL6, IL8, and tumor necrosis factor (TNF)A, blood coagulation-related genes SERPINE1, tissue factor (TF), and thrombopoietin (TM), and fibrinolysis-related gene tissue-type plasminogen activator (t-PA) was analyzed using quantitative real-time PCR.
IL1B, IL8, SERPINE1, TF, and TM expression in HAoEC was significantly reduced in the culture medium of super-low dose (0.1 ng/ml) LPS-activated macrophages.
Super-low dose LPS-activated macrophages can suppress vascular endothelial cell inflammation and may be useful in preventing various diseases caused by the dysfunction of activated vascular endothelial cells.
背景/目的：血管内皮细胞在调节免疫反应和维持凝血与纤溶平衡方面发挥着重要作用。激活的巨噬细胞和血管内皮细胞产生的炎症细胞因子过度激活血管内皮细胞，导致凝血和纤溶相关因子的表达失衡。血管内皮细胞功能障碍可导致多种疾病的发生。先前的研究表明，低剂量脂多糖（LPS）激活的巨噬细胞培养基可以抑制脂肪细胞中炎症细胞因子的表达增加。抑制低剂量 LPS 激活的巨噬细胞中炎症细胞因子基因的表达可能有助于调节血管内皮细胞的功能障碍。
用佛波醇 12-肉豆蔻酸 13-乙酸酯（PMA）将人单核细胞 THP-1 细胞分化为巨噬细胞，并用 LPS 激活。将 LPS 激活的 THP-1 的培养基添加到人主动脉内皮细胞（HAoEC）中。五天后，使用定量实时 PCR 分析炎症细胞因子基因白细胞介素（IL）1B、IL6、IL8 和肿瘤坏死因子（TNF）A、血液凝固相关基因丝氨酸蛋白酶抑制剂 E1（SERPINE1）、组织因子（TF）和血小板生成素（TM）以及纤溶相关基因组织型纤溶酶原激活物（t-PA）的表达。
HAoEC 中 IL1B、IL8、SERPINE1、TF 和 TM 的表达在超低剂量（0.1ng/ml）LPS 激活的巨噬细胞培养基中显著降低。
超低剂量 LPS 激活的巨噬细胞可以抑制血管内皮细胞炎症，可能有助于预防由激活的血管内皮细胞功能障碍引起的各种疾病。
