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.
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-kappaB) 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 microg/mL (CRP groups) for 24 h. In PDTC (a specific NF-kappaB inhibitor) group, the cells were pre-treated with PDTC at 10 micromol/L and then with 100 microg/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-kappaB inhibitor alpha (IkappaB-alpha) and NF-kappaB P(65) 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 IkappaB-alpha expression was decreased in the cells with the concentrations of CRP and ELISA demonstrated that NF-kappaB P65 expression in the CRP-induced cells was increased. After pre-treatment of the cells with PDTC at 10 micromol/L, the decrease in IkappaB-alpha expression and the increase in NF-kappaB P(65) 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-kappaB. Down-regulation of the expression and activity of MMP-9 may be a new treatment alternative for plaque stabilization by inhibiting the NF-kappaB activation.
Sheng
Fuqiang
F
Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. shengfq1129@hotmail.com
Cheng
Longxian
L
Zeng
Qiutang
Q
Gao
Wen
W
D002097:C-Reactive Protein / Q000494:pharmacology*; D002460:Cell Line; D006801:Humans; D020672:I-kappa B Proteins / Q000494:pharmacology; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D009000:Monocytes / Q000166:cytology / Q000378:metabolism*; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D011392:Proline / Q000031:analogs & derivatives / Q000494:pharmacology; D013859:Thiocarbamates / Q000494:pharmacology
D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D013859:Thiocarbamates; C066229:prolinedithiocarbamate; D000072000:NF-KappaB Inhibitor alpha; D002097:C-Reactive Protein; D011392:Proline; D020780:Matrix Metalloproteinase 9