MAPK和NF-κB通路抑制剂对IL-1β诱导滑膜细胞MMP-2活性的影响  

Effects of MAPK or NF-κB pathway inhibitors on IL-1β-induced matrix metallo-proteinase-2 activity in synovial cells

作　　者：陈荣富[1] 黄伟[1] 谢静[2] 梁熙[1] KL Paul Sung 王春莉[2] 符纯锋[1] 

机构地区：[1]重庆医科大学附属第一医院骨科,重庆400016 [2]重庆大学生物工程学院与国家"111计划"基地,重庆400044 [3]美国加州大学圣迭亚哥分校骨科与生物工程系

出　　处：《第三军医大学学报》2012年第17期1741-1744,共4页Journal of Third Military Medical University

基　　金：重庆市卫生局医学科研项目(2011-2-054)~~

摘　　要：目的研究白介素-1β(Interleukin-1β,IL-1β)对人膝关节滑膜细胞基质金属蛋白酶-2(Matrix metalloprotein-ase-2,MMP-2)活性的影响及MAPK和NF-κB信号通路抑制剂对该过程的影响。方法用不同浓度的IL-1β处理体外培养的滑膜细胞72 h,明胶酶谱法检测细胞培养液中MMP-2的活性;选取10 ng/ml的IL-1β单独或分别与4种信号通路抑制剂(NF-κB抑制剂Bay11-7082,MAPK抑制剂SB203580、PD98059和SP600125)处理滑膜细胞,处理后12、24、48、72 h检测MMP-2的活性。结果 IL-1β随浓度和处理时间的增加明显上调滑膜细胞MMP-2的活性(P<0.05);与IL-1β处理组比较,Bay11-7082明显抑制了IL-1β诱导MMP-2活性的上调,并使72 h时MMP-2的活性降至13%(P<0.01);其他抑制剂对IL-1β诱导MMP-2活性上调的影响无统计学差异(P>0.05)。结论 IL-1β以时间和剂量依赖方式,通过NF-κB信号通路诱导滑膜细胞MMP-2活性。Objective To study the effects of interlukin-1β（IL-1β） on the activity of matrix metalloproteinase-2（MMP-2） in synovial cells from human knee joint,and the effects of MAPK or NF-κB signal pathway inhibitors on IL-1β-induced MMP-2 activity.Methods In vitro cultured synovial cells were treated with IL-1β at different concentrations,and gelatin zymography was performed to detect MMP-2 activity at 72 h.IL-1β of 10 ng/ml alone or in combination with each of four signal pathway inhibitors（NF-κB inhibitor： Bay11-7082;MAPK inhibitor： SB203580,PD98059 and SP600125） were used to treat the synovial cells,and MMP-2 activity was detected at 12,24,48 and 72 h,respectively.Results IL-1β significantly increased MMP-2 activity in synovial cells with increased concentration or time（P0.05）.Bay11-7082 dramatically inhibited IL-1β-stimulated MMP-2 activity,and the activity was decreased to 13% compared with the IL-1β group（P0.01）.However,other inhibitors had no significant effect on the IL-1β-stimulated MMP-2 activity（P0.05）.Conclusion IL-1β significantly increases MMP-2 activity through NF-κB signal pathway in synovial cells in a dose-and time-dependent manner.

关 键 词：白介素-1Β 滑膜细胞 基质金属蛋白酶-2 NF-κB 

分 类 号：R392.11[医药卫生—免疫学] R392.3[医药卫生—基础医学]