内脏脂肪素对巨噬细胞中EMMPRIN表达的影响及其机制的探讨
Effect and mechanism of visfatin activity on EMMPRIN expression in macrophages
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摘要: 目的: 研究内脏脂肪素（visfatin,Vis）对巨噬细胞细胞外基质金属蛋白酶诱导因子(EMMPRIN)表达的影响及其机制。方法: 诱导THP-1单核细胞转化为巨噬细胞后，加入Vis，用RT-PCR和Western blot分别测定EMMPRIN基因和其蛋白的表达。以丝裂原活化蛋白激酶（MAPK）信号通路抑制剂、视黄醛X受体（RXR）配体及过氧化物酶增殖体活化受体γ（PPARγ）配体预处理巨噬细胞后,加入Vis,检测上述抑制剂及配体对Vis刺激效果的作用。以Vis刺激巨噬细胞，检测Vis对MAPK通路激活及对PPARγ蛋白表达的作用。结果: Vis刺激组，EMMPRIN基因及其蛋白的水平均明显增高，与对照组相比具有统计学差异（P<0.05，P<0.01）。p38 MAPK、ERK1/2 MAPK通路抑制剂及RXR配体可抑制Vis对EMMPRIN表达的促进作用。Vis可促进38 MAPK及ERK1/2 MAPK的磷酸化。结论: Vis可增加巨噬细胞炎症因子的表达，该过程同p38 MAPK及ERK1/2 MAPK通路的磷酸化相关。RXR可能参与了该过程。Abstract: AIM: To investigate the effect and mechanism of visfatin on extracellular matrix metalloproteinase inducer (EMMPRIN) expression in macrophages. METHODS: Thp-1 derived macrophages were stimulated with different concentrations of visfatin. EMMPRIN mRNA and protein expression were assayed by RT-PCR and Western blot. For inhibition study, cells were pretreated with MAPK inhibitors, retinoid x receptor(RXR) ligand and nuclear transcription factor peroxisome proliferator-activated receptorγ (PPARγ) ligand prior to incubation with visfatin for 24 h. Cells were also stimulated with different concentrations of visfatin to investigate the effect of visfatin on MAPK activation and PPARγ expression. RESULTS: Visfatin significantly enhanced EMMPRIN mRNA and protein expression in macrophages. p38 and ERK1/2 MAPK inhibitors as well as RXR ligand blocked this activity. Visfatin activated p38 and ERK1/2 MAPK. CONCLUSION: Visfatin enhances macrophage expression of inflammatory factors, which require p38 and ERK1/2 MAPK. RXR may mediate this activity.
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