Chang Ya-Ying, Yang Chen-Hsien, Wang Shih-Ching, Kao Ming-Chang, Tsai Pei-Shan, Huang Chun-Jen
Department of Anesthesiology, Taipei Tzu Chi Hospital, Taipei, Taiwan; School of Medicine, Tzu Chi University, Hualien, Taiwan.
Graduate Institute of Nursing, College of Nursing, Taipei Medical University, Taipei, Taiwan.
J Surg Res. 2015 Aug;197(2):412-8. doi: 10.1016/j.jss.2015.04.042. Epub 2015 Apr 18.
Vasopressin possesses potent anti-inflammatory effects. Endotoxin recognition (mediated by cluster of differentiation 14 [CD14]), endotoxin binding, and subsequent nuclear factor-κB (NF-κB) activation are essential mechanisms for initiation of the inflammatory response. We elucidated the effects of vasopressin on these essential mechanisms of inflammation with the hypothesis that vasopressin could inhibit CD14 expression, endotoxin binding, and NF-κB activation in activated macrophages.
Murine macrophage-like cell line RAW264.7 cells were stimulated with endotoxin (lipopolysaccharide [LPS]; 100 ng/mL) or LPS plus vasopressin (1000 pg/mL; designated as the LPS and the LPS + V groups, respectively). After reaction, between-group differences in inflammatory molecule concentrations and levels of NF-κB activation, endotoxin-macrophages binding, and CD14 expression were compared. Analysis of variance was performed for statistical analysis.
The concentrations of chemokine macrophage inflammatory protein 2 and cytokine interleukin 6 of the LPS + V group were significantly lower than those of the LPS group (P = 0.004 and P < 0.001). The nuclear concentration of phosphorylated NF-κB p65 and cytosolic concentration of phosphorylated inhibitor-κBα of the LPS + V group were significantly lower than those of the LPS group (all P < 0.05). In addition, the level of endotoxin-macrophages binding of the LPS + V group was significantly lower than that of the LPS group (P < 0.001). The level of surface CD14 expression of the LPS + V group was also significantly lower than that of the LPS group (P = 0.019).
This study confirmed the potent anti-inflammatory effects of vasopressin. The mechanisms underlying the anti-inflammatory effects of vasopressin may involve its effects on inhibiting CD14 expression, endotoxin binding, and subsequent NF-κB activation.
血管加压素具有强大的抗炎作用。内毒素识别（由分化簇14 [CD14]介导）、内毒素结合以及随后的核因子-κB（NF-κB）激活是启动炎症反应的重要机制。我们以血管加压素可抑制活化巨噬细胞中CD14表达、内毒素结合及NF-κB激活这一假设，阐明了血管加压素对这些炎症关键机制的影响。
用内毒素（脂多糖[LPS]；100 ng/mL）或LPS加血管加压素（1000 pg/mL；分别指定为LPS组和LPS + V组）刺激小鼠巨噬细胞样细胞系RAW264.7细胞。反应后，比较各组间炎症分子浓度以及NF-κB激活水平、内毒素与巨噬细胞结合情况和CD14表达的差异。采用方差分析进行统计学分析。
LPS + V组趋化因子巨噬细胞炎性蛋白2和细胞因子白细胞介素6的浓度显著低于LPS组（P = 0.004和P < 0.001）。LPS + V组磷酸化NF-κB p65的核浓度和磷酸化抑制蛋白κBα的胞质浓度显著低于LPS组（所有P < 0.05）。此外，LPS + V组内毒素与巨噬细胞的结合水平显著低于LPS组（P < 0.001）。LPS + V组表面CD14表达水平也显著低于LPS组（P = 0.019）。
本研究证实了血管加压素强大的抗炎作用。血管加压素抗炎作用的潜在机制可能涉及其对抑制CD14表达、内毒素结合及随后NF-κB激活的作用。
