The relation between the expression and activity of MMP-9 in C-reactive protein （CRP）-induced human THP-1 mononuclear cells and the activation of nuclear factor kappa-B （NF-κB） was studied to investigate the poss...The relation between the expression and activity of MMP-9 in C-reactive protein （CRP）-induced human THP-1 mononuclear cells and the activation of nuclear factor kappa-B （NF-κB） was studied to investigate the possible role of CRP in plaque destabilization. Human THP-1 cells were incubated in the presence of CRP at 0 （control group）, 25, 50 and 100 μg/mL （CRP groups） for 24 h. In PDTC （a specific NF-κB inhibitor） group, the cells were pre-treated with PDTC at 10 μmol/L and then with 100 μg/mL CRP. The conditioned media （CM） and human THP-1 cells in different groups were harvested. MMP-9 expression in CM and human THP-1 cells was measured by ELISA and Western blotting. MMP-9 activity was assessed by fluorogenic substrates. The expression of NF-κB inhibitor α （IκB-α） and NF-κB p65 was detected by Western blotting and ELISA respectively. The results showed that CRP increased the expression and activity of MMP-9 in a dose-dependent manner in the human THP-1 cells. Western blotting revealed that IiB-α expression was decreased in the cells with the concentrations of CRP and ELISA demonstrated that NF-κB p65 expression in the CRP-induced cells was increased. After pre-treatment of the cells with PDTC at 10 μmol/L, the decrease in IκB-α expression and the increase in NF-κB p65 expression in the CRP-induced cells were inhibited, and the expression and activity of MMP-9 were lowered too. It is concluded that increased expression and activity of MMP-9 in CRP-induced human THP-1 cells may be associated with activation of NF-κB. Down-regulation of the expression and activity of MMP-9 may be a new treatment alternative for plaque stabilization by inhibiting the NF-κB activation.展开更多
目的:探讨分化抑制因子1(inhibitor of differentiation-1,ID1)基因在急性髓系白血病(acute myeloid leukemia,AML)患者骨髓单个核细胞中的表达及其临床意义。方法:应用实时定量PCR方法检测153例初诊AML患者骨髓单个核细胞ID1基因的转...目的:探讨分化抑制因子1(inhibitor of differentiation-1,ID1)基因在急性髓系白血病(acute myeloid leukemia,AML)患者骨髓单个核细胞中的表达及其临床意义。方法:应用实时定量PCR方法检测153例初诊AML患者骨髓单个核细胞ID1基因的转录本水平。结果:ID1基因的表达范围为0.000~3.536(中位为0.030)。以中位数值为界将AML患者分为高表达组和低表达组,两组AML患者性别、外周血小板计数以及常见基因突变无统计学差异(P>0.05),外周血白细胞计数、外周血血红蛋白、FAB分型、WHO分型、核型分组及核型危险程度分组趋近统计学差异(P<0.10)。ID1高表达患者年龄以及骨髓原始细胞比例显著高于ID1低表达患者(P=0.033、0.035)。ID1高表达组患者经治疗后完全缓解率低于ID1低表达组(P<0.01),且定量分析显示经1~2个疗程诱导化疗获得完全缓解的AML患者初诊时ID1表达水平显著低于未获得完全缓解的AML患者(P=0.001)。生存分析显示在全部患者、非M3患者或正常核型AML患者中,ID1高表达患者总体生存时间均明显短于ID1低表达患者(P=0.002、0.008和0.050)。结论:ID1基因表达水平可作为AML患者化疗反应以及预后判断的分子标志。展开更多
文摘The relation between the expression and activity of MMP-9 in C-reactive protein （CRP）-induced human THP-1 mononuclear cells and the activation of nuclear factor kappa-B （NF-κB） was studied to investigate the possible role of CRP in plaque destabilization. Human THP-1 cells were incubated in the presence of CRP at 0 （control group）, 25, 50 and 100 μg/mL （CRP groups） for 24 h. In PDTC （a specific NF-κB inhibitor） group, the cells were pre-treated with PDTC at 10 μmol/L and then with 100 μg/mL CRP. The conditioned media （CM） and human THP-1 cells in different groups were harvested. MMP-9 expression in CM and human THP-1 cells was measured by ELISA and Western blotting. MMP-9 activity was assessed by fluorogenic substrates. The expression of NF-κB inhibitor α （IκB-α） and NF-κB p65 was detected by Western blotting and ELISA respectively. The results showed that CRP increased the expression and activity of MMP-9 in a dose-dependent manner in the human THP-1 cells. Western blotting revealed that IiB-α expression was decreased in the cells with the concentrations of CRP and ELISA demonstrated that NF-κB p65 expression in the CRP-induced cells was increased. After pre-treatment of the cells with PDTC at 10 μmol/L, the decrease in IκB-α expression and the increase in NF-κB p65 expression in the CRP-induced cells were inhibited, and the expression and activity of MMP-9 were lowered too. It is concluded that increased expression and activity of MMP-9 in CRP-induced human THP-1 cells may be associated with activation of NF-κB. Down-regulation of the expression and activity of MMP-9 may be a new treatment alternative for plaque stabilization by inhibiting the NF-κB activation.
文摘目的:探讨分化抑制因子1(inhibitor of differentiation-1,ID1)基因在急性髓系白血病(acute myeloid leukemia,AML)患者骨髓单个核细胞中的表达及其临床意义。方法:应用实时定量PCR方法检测153例初诊AML患者骨髓单个核细胞ID1基因的转录本水平。结果:ID1基因的表达范围为0.000~3.536(中位为0.030)。以中位数值为界将AML患者分为高表达组和低表达组,两组AML患者性别、外周血小板计数以及常见基因突变无统计学差异(P>0.05),外周血白细胞计数、外周血血红蛋白、FAB分型、WHO分型、核型分组及核型危险程度分组趋近统计学差异(P<0.10)。ID1高表达患者年龄以及骨髓原始细胞比例显著高于ID1低表达患者(P=0.033、0.035)。ID1高表达组患者经治疗后完全缓解率低于ID1低表达组(P<0.01),且定量分析显示经1~2个疗程诱导化疗获得完全缓解的AML患者初诊时ID1表达水平显著低于未获得完全缓解的AML患者(P=0.001)。生存分析显示在全部患者、非M3患者或正常核型AML患者中,ID1高表达患者总体生存时间均明显短于ID1低表达患者(P=0.002、0.008和0.050)。结论:ID1基因表达水平可作为AML患者化疗反应以及预后判断的分子标志。
