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| CD40配体通过诱导型环氧合酶途径诱导单核巨噬细胞分泌基质金属蛋白酶 |
| 樊民,李岚,吴宗贵,黄佐,任雨笙,潘晓明 |
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| (第二军医大学长征医院心内科,上海,200003;中国人民解放军第411医院内4科,上海,200081) |
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| 摘要: |
| 目的:观察重组人CD40配体(rhCD40L)对U937细胞分泌基质金属蛋白酶(MMPs)的影响,探讨其可能的作用机制.方法:不同浓度(0.1、0.2、0.4 μg/ml)的rhCD40L和不同浓度(10-5、10-4、10-3 mol/L)的NS-398(COX-2特异性抑制剂)分别刺激体外培养的U937细胞24 h后收集上清液;在加入终浓度为0.4 μg/ml rhCD40L的基础上,分别加入终浓度为10-4 mol/L的阿司匹林(COX-1抑制剂)或NS-398,共同刺激U937细胞24 h后收集上清液.酶谱法测定上述U937细胞培养上清中MMPs活性.结果:rhCD40L可使MMP-2和MMP-9活性增加(P＜0.01),且随浓度的增加而逐渐增强,0.4 μg/ml rhCD40L作用最强;NS-398可抑制MMP-2和MMP-9的活性,且抑制作用随剂量的增加而增强(P＜0.05).NS-398、阿司匹林均可抑制rhCD40L诱导U937细胞分泌MMP-2和MMP-9(P＜0.01),NS-398的抑制作用强于阿司匹林(P＜0.05).结论:rhCD40L以浓度依赖的方式诱导单核巨噬细胞分泌MMPs,这种诱导作用可能与诱导型环氧合酶(COX)有关,而且与COX-2的相关性可能较COX-1更密切. |
| 关键词: CD40配体、诱导型环氧合酶、基质金属蛋白酶、巨噬细胞 |
| DOI：10.3724/SP.J.1008.2006.00845 |
| 投稿时间：2005-12-13修订日期：2006-05-10 |
| 基金项目: |
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| rhCD40L induces mononuclear macrophages secreting matrix metalloproteinases through cyclooxygenase-2 pathway |
| FAN Min,LI Lan,WU Zong-gui,HUANG Zuo,REN Yu-sheng,PAN Xiao-ming |
| (第二军医大学长征医院心内科,上海,200003;中国人民解放军第411医院内4科,上海,200081) |
| Abstract: |
| Objective：To evaluate the influence of rhCD40L on mononuclear macrophage, U937 cells, secreting matrix metalloproteinases （MMPs） and its possible mechanism. Methods： U937 cells were treated with different concentrations of rhCD40L and NS-398 （specific antagonist of COX-2） for 24 h and the supernatants were harvested. Cells treated with 0.4 μg/ml rhCD40L were further treated with 10^-4 mol/L NS-398 or aspirin separately for 24 h and the supernatants were harvested. Zymography was used to determine the activities of MMPs in the above supernatants. Results： rhCD40L increase the activity of MMP-2 and MMP-9 in a dose-dependent manner （P〈0.01） ; the increased peaked when rhCD40L was at 0.4 μg/ml. NS-398 inhibited the activity of MMP-2 and MMP-9 in a dose-dependent manner （P〈0.05）. NS-398 and aspirin both significantly inhibited the activity of MMP-2 and MMP-9 induced by rhCD40L （P〈0.05）. Conclusion： rhCD40L can induce U937 cells to secrete MMPs in a dose dependent manner, which might be related to COX, more possibly through COX-2 than COX-1 pathway |
| Key words: CD40 ligand cyclooxygenase-2 matrix metalloproteinases macrophages |
