血管紧张素Ⅱ激活巨噬细胞株p38MAPK信号通路并诱导其增殖

Angiotensin Ⅱ stimulates p38MAPK phosphorylation and proliferation of macrophage cell line

目的:探讨血管紧张素Ⅱ(AngⅡ)激活巨噬细胞p38MAPK信号通路的模式变化及其对巨噬细胞株增殖的影响。方法:用Westernblot测定细胞p38MAPK磷酸化表达;用细胞免疫组化观察细胞p38MAPK激活后核移位;用MTT法观察细胞增殖。结果:AngⅡ(1μmol/L)可诱导RAW264.7细胞p38MAPK磷酸化表达,15-30分钟达到高峰,随时间呈峰形变化。AngⅡ呈剂量依赖性诱导RAW264.7细胞p38MAPK磷酸化。p38MAPK特异性抑制剂SB202190可显著抑制RAW264.7细胞p38MAPK磷酸化,并呈剂量依赖性。AngⅡ可诱导RAW264.7细胞增殖,SB202190可显著抑制AngⅡ诱导的RAW264.7细胞增殖。结论:AngⅡ可激活RAW264.7巨噬细胞株p38MAPK信号通路,并通过p38MAPK信号通路调控RAW264.7细胞增殖。

Objective:To investigate the changes of p38 mitogen-activated protein kinase(p38MAPK) phosphorylation induced by angiotensin Ⅱ(AngⅡ) in RAW264.7 macrophages, and to determine the activation of p38MAPK signaling induced by AngⅡ with specific inhibitor of p38MAPK, SB202190, and also to investigate the effect of AngⅡ on RAW264.7 macrophage proliferation. Methods: Western blot was used for examining the p38MAPK phosphorylation, and the nuclear translocation of phosphorylated p38MAPK was detected by immunohis tochemical staining. MTT was used for examining the cell proliferation.Results:Following excitation by AngⅡ(1 μmol/L) in vitro, there was substantial up-regulation of p38MAPK phosphorylation in RAW264.7 macrophages with maximal activation at 15-30 min; and marked nuclear translocation of phosphorylated p38MAPK was also happened at 15-30 min. AngⅡ enhanced the expression of p38MAPK phosphorylation in RAW264.7 macrophages in a dose-dependent manner. Pre-treatment with SB202190(1,5 μmol/L) for 30 min in RAW264.7 macrophages before AngⅡ(1 μmol/L) used, the expression of p38MAPK phosphorylation was inhibited markedly in a dose-dependent manner. AngⅡ increased the cell proliferation in vitro, and pretreatment of SB202190 reduced the cell proliferation induced by AngⅡ.Conclusion: Angiotensin Ⅱ may induce phosphorylation of p38MAPK in RAW264.7 macrophages, and the activation of p38MAPK may regulate the proliferation of RAW264.7 macrophages.