白介素-10抑制TNF-α诱导的血管平滑肌细胞增殖

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

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p4 4 /p4 2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 (vascularsmoothmusclecells,VSMCs)的增殖状态 ;应用流式细胞术测定细胞周期 ;利用p4 4 / 4 2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 0 5 )。rhIL 10单独应用对VSMCs生长没有影响 (P >0 0 5 )。在TNF α刺激下 ,低至 10ng/ml的rhIL 10可抑制VSMCs的生长 (P <0 0 5 )。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期 ,与对照组相比有明显差异 (P <0 0 1)。 ( 2 )TNF α对p4 4 /p4 2MAPK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p4 4 /p4

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 or TNF α respectively, and then cotreated with rhIL 10 and 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 growth, but significantly inhibited VSMC proliferation induced by TNF α at a dose of 10 ng/ml. The cell number in G 0/G 1 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.