白介素-10抑制TNF-α 诱导的血管平滑肌细胞增殖

 
 


欧阳平, 彭立胜, 杨红, 吴文言, 徐安龙*
(
中山大学生命科学学院, 广州  510275)

摘 要: 
研究观察了重组人白介素
-10 (rhIL-10)对肿瘤坏死因子(TNF-α)刺激的离体大鼠胸主动脉血管平滑肌细胞增殖、 细胞周期及对p44/p42 丝裂素活化蛋白激酶的影响。实验培养大鼠主动脉血管平滑肌细胞, 采用MTS/PES法确定血管平滑肌细胞(vascular smooth muscle cells,  VSMCs)的增殖状态; 应用流式细胞术测定细胞周期; 利用p44/42磷酸化抗MAPK抗体的蛋白免疫印迹法测定MAPK蛋白表达。结果显示: (1) TNF-α处理组与对照组相比, TNF-α对VSMC增殖具有明显的刺激作用(P<0.05)rhIL-10单独应用对VSMCs生长没有影响(P>0.05)。在TNF-α刺激下, 低至10 ng/mlrhIL-10可抑制VSMCs的生长 (P<0.05)。流式细胞术测定的结果显示, rhIL-10分别可使TNF-α作用下的VSMC大部分处于G0/G1, 与对照组相比有明显差异(P<0.01)(2) TNF-α对p44/p42 MAPK蛋白表达有显著的增强作用, 此作用可被rhIL-10抑制。结果提示, rhIL-10可抑制TNF-α诱导的VSMC增殖及p44/p42 丝裂素活化蛋白激酶的表达。
 

关键词
平滑肌
, 血管白介素-10; 丝裂素活化蛋白激酶; 细胞增殖
学科分类号: 
R541

 

 
 

 

 
 

Recombinant human interleukin-10 inhibits vascular smooth muscle cell proliferation induced by TNF-α

OUYANG Ping, PENG Li-Sheng, YANG Hong, WU Wen-Yan, XU An-Long*
(College of Life Science, Zhong Shan University, Guangzhou 510275)

Abstract:
Vessel injury provokes a release in proinflammatory cytokines that influence vascular smooth muscle cell (VSMC) proliferation. The purposes of  this study was to determine the effects of recombinant human interleukin-10 (rhIL-10) on rat vascular smooth muscle cell proliferation and the activity of p44/p42 mitogen-activated protein kinase (MAPK) promoted by tumor necrosis factor-
α (TNF-α).  Rat aortic VSMCs were cultured and treated with rhIL-10 with or without TNF-α. The proliferation of VSMCs was quantified by colormetric assay. Cell cycle analysis was performed by flow cytometry. The p44/42 MAPK activity was evaluated by the immunoblotting technique using anti-p44/42 phospho-MAPK antibody.  Compared to control group, TNF-α  stimulated significantly VSMC proliferation in  TNF-α group. rhIL-10 alone had no effect on VSMC gro
wth, but  significantly inhibited VSMC proliferation induced by TNF-
α at a dose of 10 ng/ml.  The cell number in G0/G1 phase of TNF-α and rhIL-10 co-treatment group was higher than that of TNF-α group (P<0.01) by flow cytometry analysis.  The p44/42 MAPK activity was significantly enhanced by TNF-α and the TNF-α effect was opposed by rhIL-10.   It is suggested that  rhIL-10 can inhibit TNF-α induced VSMC proliferation and phosphorylation of p44/42 MAPK.

Key words:
 vascular smooth muscle; interleukin-10; mitogen-activated protein kinase; cell proliferation

 
     
     
 

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