MMP-9在THP-1分化过程中的表达及调节

The Expression and regulation of MMP-9 During THP-1 Cell Differentiation

基质金属蛋白酶 - 9(MMP- 9)主要降解基底膜中的 和 型胶原 ,在细胞穿经基底膜的过程中起关键的作用。为探讨前单核细胞 THP- 1分化过程中 MMP- 9的表达及其信号传导途径 ,作者采用细胞粘附实验、流式细胞术和凋亡检测的方法 ,检测了佛波脂 (PMA)诱导 THP- 1分化过程中 ,PKC、PI3K、NF- κB抑制剂 CalphostinC、L Y2 940 0 2、PDTC和地塞米松对细胞粘附、MMP- 9表达及细胞凋亡的影响。结果表明 :在 THP- 1分化过程中有MMP- 9的表达 ,各种抑制剂及地塞米松可抑制细胞粘附及 MMP- 9的表达 ,Annexin V凋亡检测发现 PDTC是以诱导细胞凋亡的方式而发挥作用的。因此 ,MMP- 9可作为前单核细胞向单核细胞分化的标志 ,PKC、PI3K、NF- κB都参与了 MMP- 9上调的信号传导。抑制 MMP- 9的表达将有助于炎性细胞浸润性疾病的治疗。

The function of Matrix Metalloproteinase 9(MMP 9) is to take part in the degradation of type Ⅳ collagen and type Ⅴ collagen, which are the main composition of basement membrane. This study was aimed to investigate the expression and regulation of MMP 9 during pre monocyte THP 1 differentiation. The effects of PKC inhibitor Calphostin C, PI3K inhibitor LY294002, NF κB inhibitor PDTC, and dexamethasone on cell adhesion, MMP 9 expression and cell apoptosis were determined by cell adhesion test, flow cytometry and apoptosis detecting. The results showed that the expression of MMP 9 incerased during THP 1 differentiation. All of the inhibitors and dexamethasone inhibited THP 1 adhesion and MMP 9 expression. PDTC induced THP 1 apoptosis. So, MMP 9 could be a marker of THP 1 differentiation. All of PKC, PI3K, NF κB took part in the signal transduction of MMP 9 upregulation. These findings indicate that inhibition of MMP 9 and NF κB can be used in the treatment of diseases caused by excess inflammatory cells infiltration.