诱导型环氧合酶-2在CD40配体诱导基质金属蛋白酶表达中的作用

rhCD40L induces expression of matrix metalloproteinases in cultured U937 cells by cyclooxygenase-2 pathway

目的:探讨重组人CD40配体(rhCD40L)诱导U937细胞中基质金属蛋白酶(MMPs)表达的作用及其与诱导型环氧合酶-2(COX-2)途径的关系。方法:体外培养U937细胞,以不同浓度(0.1、0.2、0.4 mg/L)的rhCD40L和不同浓度(10-5 mol/L、10-4 mol/L、10-3 mol/L)的COX-2特异性抑制剂(NS-398)分别刺激24 h。在加入终浓度为0.4 mg/L rhCD40L的基础上,加入终浓度为10-4 mol/L的NS-398,共同刺激U937细胞24 h后,收集培养上清液,用酶谱法测定MMPs的活性。结果:rhCD40L可使MMP-2和MMP-9的活性明显增加(P<0.01),且呈剂量依赖性;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)。结论:rhCD40L以浓度依赖的方式诱导MMPs表达,rhCD40L对MMPs的诱导作用可能与COX-2途径有关。

AIM： To evaluate matrix metalloproteinase（MMP） expression induced by rhCD40L in cultured U937 cell and possible effects of cyclooxygenase-2（COX-2）.METHODS： U937 cells were treated with rhCD40L and NS-398 in different concentrations,respectively,and on the basis of the treatment with rhCD40L,U937 cells were cocultured with NS-398 and aspirin.The supernatant of the U937 cells cultures was collected.Zymography was performed by SDS-PAGE in 10% gels containing 0.1%（w/v） gelatin（denatured collagen） at 4℃.The activities of MMPs were detected by the grey level of the band.RESULTS： rhCD40L increased the activity of MMPs in a dose-dependent manner,whereas NS-398 significantly inhibited the activity of MMPs.NS-398 significantly inhibited the activity of MMPs induced by rhCD40L.CONCLUSION： rhCD40L can induce U937 cells to secrete MMPs in a dose-dependent manner,which may be related to COX-2 pathway.