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
目的分析人附睾分泌蛋白4(human epididymis protein 4,HE4)、糖类抗原125(carbohydrate antigen 125,CA125)、高迁移率族蛋白A2(high mobility group protein A2,HMGA2)、基质金属蛋白酶-1(matrix metalloproteinase-1,MMP-1)及卵巢癌...目的分析人附睾分泌蛋白4(human epididymis protein 4,HE4)、糖类抗原125(carbohydrate antigen 125,CA125)、高迁移率族蛋白A2(high mobility group protein A2,HMGA2)、基质金属蛋白酶-1(matrix metalloproteinase-1,MMP-1)及卵巢癌风险预测模型(risk of ovarian malignancy algorithm,ROMA)指数在卵巢癌诊断中的应用价值。方法选取2020年1月至2022年5月海南省海口市中医医院收治并经病理证实的100例卵巢癌患者作为恶性卵巢肿瘤组,并以同期收治的100例良性卵巢肿瘤患者作为良性卵巢肿瘤组、100例健康体检女性作为对照组,检测HE4、CA125、HMGA2、MMP-1水平,计算ROMA指数,比较三组上述指标的差异,并绘制受试者工作特征(receiver operating characteristic,ROC)曲线评估HE4、CA125、HMGA2、MMP-1和ROMA指数对卵巢癌的诊断价值。结果恶性卵巢肿瘤组血清HE4、CA125、HMGA2、MMP-1水平高于良性卵巢肿瘤组和对照组,良性卵巢肿瘤组血清CA125、HMGA2水平高于对照组(P<0.05),而血清HE4、MMP-1水平与对照组比较差异无显著性(P>0.05)。ROC曲线分析显示,HE4、CA125、HMGA2、MMP-1联合诊断卵巢癌的敏感度为83.00%,曲线下面积为0.787,均高于各项单独检测;ROMA指数诊断卵巢癌的敏感度为86.00%,曲线下面积为0.832,高于HE4、CA125、HMGA2、MMP-1联合诊断;HE4、CA125、HMGA2、MMP-1及ROMA指数联合诊断卵巢癌的敏感度为96.00%,曲线下面积为0.931,高于HE4、CA125、HMGA2、MMP-1联合及ROMA指数单独诊断(P<0.05)。结论血清HE4、CA125、HMGA2、MMP-1水平联合ROMA指数对卵巢癌的诊断价值较高,有利于卵巢癌的早期诊断及治疗,值得临床应用。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.
文摘目的分析人附睾分泌蛋白4(human epididymis protein 4,HE4)、糖类抗原125(carbohydrate antigen 125,CA125)、高迁移率族蛋白A2(high mobility group protein A2,HMGA2)、基质金属蛋白酶-1(matrix metalloproteinase-1,MMP-1)及卵巢癌风险预测模型(risk of ovarian malignancy algorithm,ROMA)指数在卵巢癌诊断中的应用价值。方法选取2020年1月至2022年5月海南省海口市中医医院收治并经病理证实的100例卵巢癌患者作为恶性卵巢肿瘤组,并以同期收治的100例良性卵巢肿瘤患者作为良性卵巢肿瘤组、100例健康体检女性作为对照组,检测HE4、CA125、HMGA2、MMP-1水平,计算ROMA指数,比较三组上述指标的差异,并绘制受试者工作特征(receiver operating characteristic,ROC)曲线评估HE4、CA125、HMGA2、MMP-1和ROMA指数对卵巢癌的诊断价值。结果恶性卵巢肿瘤组血清HE4、CA125、HMGA2、MMP-1水平高于良性卵巢肿瘤组和对照组,良性卵巢肿瘤组血清CA125、HMGA2水平高于对照组(P<0.05),而血清HE4、MMP-1水平与对照组比较差异无显著性(P>0.05)。ROC曲线分析显示,HE4、CA125、HMGA2、MMP-1联合诊断卵巢癌的敏感度为83.00%,曲线下面积为0.787,均高于各项单独检测;ROMA指数诊断卵巢癌的敏感度为86.00%,曲线下面积为0.832,高于HE4、CA125、HMGA2、MMP-1联合诊断;HE4、CA125、HMGA2、MMP-1及ROMA指数联合诊断卵巢癌的敏感度为96.00%,曲线下面积为0.931,高于HE4、CA125、HMGA2、MMP-1联合及ROMA指数单独诊断(P<0.05)。结论血清HE4、CA125、HMGA2、MMP-1水平联合ROMA指数对卵巢癌的诊断价值较高,有利于卵巢癌的早期诊断及治疗,值得临床应用。
