Increased Expression and Activity of MMP-9 in C-reactive Protein- induced Human THP-1 Mononuclear Cells Is Related to Activation of Nuclear Factor Kappa-B

• Published in: Journal of Huazhong University of Science and Technology. Medical sciences 2009-08, Vol.29 (4), p.399-403
• Main Author: 盛富强 程龙献 曾秋棠 高文
• Format: Article
• Language: English
• Subjects: C-Reactive Protein - pharmacology; Cell Line; Humans; I-kappa B Proteins - pharmacology; Matrix Metalloproteinase 9 - metabolism; Medicine; Medicine & Public Health; Monocytes - cytology; Monocytes - metabolism; NF-kappa B - drug effects; NF-kappa B - metabolism; NF-kappa B - physiology; NF-KappaB Inhibitor alpha; Proline - analogs & derivatives; Proline - pharmacology; Thiocarbamates - pharmacology; 单核细胞; 基质金属蛋白酶; 核因子-κB
• ISSN: 1672-0733; 1993-1352
• DOI: 10.1007/s11596-009-0401-0

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.