National Laboratory Animal Center, National Applied Research Laboratories, Taipei, Taiwan.
Sci Rep. 2019 Dec 13;9(1):19065. doi: 10.1038/s41598-019-55281-w.
The acute phase response (APR) is a systemic first-line defense against challenges including infection, trauma, stress, and neoplasia. Alteration of acute phase protein (APP) levels in plasma is the most important change during acute phase response. C-reactive protein (CRP), which increases dramatically during inflammation onset, is an indicator of inflammation. To monitor the process of APR, we generated human CRP promoter-driven luciferase transgenic (hCRP-Luc) mice to quantify the hCRP promoter activation in vivo. The naïve female hCRP-Luc mice express low basal levels of liver bioluminescence, but the naïve male hCRP-Luc mice do not. Thus, female hCRP-Luc mice are suitable for monitoring the process of APR. The liver bioluminescence of female hCRP-Luc mice can be induced by several toll-like receptor (TLR) ligands. The expression of liver bioluminescence was highly sensitive to endotoxin stimulation in a dose-dependent manner. On-off-on bioluminescence response was noted in female hCRP-Luc mice upon two endotoxin stimulations one month apart. The LPS-induced bioluminescence of the female hCRP-Luc mice was IL-6-mediated and associated with APP alpha-1-acid glycoprotein expression. In conclusion, the female hCRP-Luc mouse is a non-invasive, sensitive and reusable reporter tool for APR.
急性期反应（APR）是机体抵抗感染、创伤、应激和肿瘤等挑战的第一道防线。急性期蛋白（APP）在血浆中的水平变化是急性期反应过程中最重要的改变。C 反应蛋白（CRP）在炎症发作时急剧增加，是炎症的一个指标。为了监测 APR 过程，我们生成了人 CRP 启动子驱动的荧光素酶转基因（hCRP-Luc）小鼠，以在体内定量检测 hCRP 启动子的激活。未致敏的雌性 hCRP-Luc 小鼠表达低水平的肝脏生物发光，但未致敏的雄性 hCRP-Luc 小鼠则没有。因此，雌性 hCRP-Luc 小鼠适合用于监测 APR 过程。几种 Toll 样受体（TLR）配体可诱导雌性 hCRP-Luc 小鼠的肝脏生物发光。肝脏生物发光的表达对内毒素刺激具有高度的剂量依赖性敏感性。雌性 hCRP-Luc 小鼠在相隔一个月的两次内毒素刺激下表现出开-关-开的生物发光反应。雌性 hCRP-Luc 小鼠中 LPS 诱导的生物发光是由 IL-6 介导的，并与 APP α-1-酸性糖蛋白表达相关。总之，雌性 hCRP-Luc 小鼠是 APR 的一种非侵入性、敏感和可重复使用的报告工具。
