Department of Dermatology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan.
Department of Pharmacotherapy, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan.
Int J Mol Sci. 2023 Aug 3;24(15):12388. doi: 10.3390/ijms241512388.
Chronic spontaneous urticaria (CSU) is characterized by daily recurring wheal and flare with itch for more than 6 weeks. The extrinsic coagulation system has been shown to be activated in correlation with CSU severity. We have reported that tissue factor (TF), a trigger of the extrinsic coagulation cascade, is synergistically expressed on vascular endothelial cells by simultaneous stimulation with TF inducers (TFI), followed by activation of the extrinsic coagulation cascade and hyper permeability in vitro. However, vascular endothelial cells are not likely to be simultaneously stimulated by multiple TFIs under physiological conditions. Therefore, in order to know whether sequential, rather than simultaneous, stimuli with interval may induce synergistic activation of TF, we investigated the time course of the priming effects of each TFI for synergistic TF expression in vascular endothelial cells (HUVECs). We stimulated HUVECs with a TFI (first stimulation) and then stimulated cells with another TFI at indicated time points (second stimulation) and detected TF expression and activity. The TF expression induced by simultaneous stimulation diminished in a few hours. However, both synergistic enhancement of TF expression and activation level of the coagulation cascade were detected even when the second stimulation was added 18 or 22 h after the first stimulation. Thus, the priming effect of TFI for synergistic TF expression may persist for a half day or longer.
慢性自发性荨麻疹（CSU）的特征是每天反复发作风团和瘙痒超过 6 周。已经表明外源性凝血系统在与 CSU 严重程度相关的情况下被激活。我们已经报告称，组织因子（TF），外源性凝血级联的触发因素，通过同时用 TF 诱导剂（TFI）刺激，在体外协同表达在血管内皮细胞上，随后外源性凝血级联和高通透性被激活。然而，在生理条件下，血管内皮细胞不太可能同时受到多种 TFI 的刺激。因此，为了了解间隔的顺序而不是同时刺激是否会诱导 TF 的协同激活，我们研究了每个 TFI 对血管内皮细胞（HUVEC）中协同 TF 表达的引发作用的时间过程。我们用 TFI 刺激 HUVEC（第一次刺激），然后在指定的时间点用另一种 TFI 刺激细胞（第二次刺激），并检测 TF 表达和活性。同时刺激诱导的 TF 表达在数小时内减少。然而，即使在第一次刺激后 18 或 22 小时添加第二次刺激，也检测到协同增强的 TF 表达和凝血级联的激活水平。因此，TFI 对协同 TF 表达的引发效应可能持续半天或更长时间。
