过氧化酶体增殖物激活型受体γ对单核或巨噬细胞中抑制蛋白及基质金属蛋白酶-1表达的调控

Effects of PPARγ on expressions of inhibitor kappa B alpha and MMP1 in human monocyte/macrophage

目的 :研究过氧化酶体增殖物激活型受体 (PPAR)γ对人类单核或巨噬细胞核因子抑制蛋白 (IkBα)和基质金属蛋白酶 1 (MMP 1 )表达的调控影响 ,探讨PPARγ在抑制炎症反应和稳定动脉粥样斑块中的作用。方法 :PPARγ配体 ( 1 5 脱氧前列腺素J2和环格列酮 )干预体外培养的U93 7细胞 ,用四唑盐 (MTT)法检测细胞活力 ,细胞免疫组化法和流式细胞法检测细胞IkBα和MMP1的表达程度。结果 :PPARγ配体在低浓度时不会影响细胞活力 (存活率 >80 % ) ;在 1、3、2 4h,PPARγ激活后均能增加IkBα在细胞内的表达 ,但是随着时间推移 ,这种作用逐渐减弱 ,与佛波醇肉豆蔻酸乙酸酯阳性组相比 ,PPARγ配体组MMP1的表达水平下降 (P <0 .0 1 )。结论 :PPARγ可能通过快速增加IkBα的表达而抑制核因子(NF κB)的活性 ,同时PPARγ可通过或不通过NF κB而抑制MMP1的表达 。

Objective: To study the effects of peroxisome proliferator activated receptor γ(PPARγ) on expressions of inhibitor kappa B alpha (IkBα) and MMP1 in human monocyte/macrophage and evaluate the functions of PPARγ pass in inhibition of inflammation response and stabilization of atherosclerosis plague. Method: Cultured U937 cells in vitro were stimulated with PMA and the liglands of PPARγ, using MTT method to test the livability of cells, and the expressions of IkBα and MMP1 were evaluated with immucytochemistry and flow cytometer method. Result: the liglands of PPARγ could not affect the cell livability at low dose (livability>80%). PPARγ could increase the expression of IkBα quickly, but the function faded out with the time's shift. Compared with PMA(+) group, the expression of MMP1 of the liglands group decreased (P< 0.01). Conculsion: PPARγ can inhibit the activity of NF-κB by increasing IkBα quickly, PPARγ can decrease the expression of MMP1 dependent or independent of NF-κB, thus may inhibit the inflammation response and stabilize the atherosclerosis plague.