Role of NFkappaB in toll-like receptor 9-mediated matrix metalloproteinase-9 expression.
- Author:
Sang Hoon LEE
1
;
Byung Rho CHIN
;
Suk Hwan BAEK
Author Information
1. Department of Dentistry, College of Medicine, Yeungnam University, Daegu, Korea.
- Publication Type:Original Article
- Keywords:
Toll-like receptor;
Matrix metalloproteinase;
NFkappaB
- MeSH:
Chloroquine;
DNA;
Luciferases;
Macrophages;
Matrix Metalloproteinase 9*;
Phosphorylation;
Real-Time Polymerase Chain Reaction;
RNA, Messenger;
Toll-Like Receptors*
- From:Journal of the Korean Association of Oral and Maxillofacial Surgeons
2007;33(6):636-642
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
BACKGROUND: CpG DNA plays an important role in immune cell function. This study examined whether the temporal control of toll-like receptor (TLR)9 by CpG DNA can regulate the expression of matrix metalloproteinase-9 (MMP-9). MeETHODS AND MATERIALS: Macrophages were cultured in the presence of 10percent FBS. For the various MMP genes analysis, RT-PCR and real-time PCR were performed. In addition, zymography assay performed for the MMP activity. The phosphorylation assay did for the ERK1/2 and NFkappaB activation, and luciferase promoter assay was for the NFkappaB activity. RESULTS: CpG DNA induced the mRNA expression of MMP-2, MMP-9, and MMP-13, but not of MMP-7, MMP-8, and MMP-12, in a time-dependent manner. Especially, the mRNA expression of MMP-9 was strongly induced by CpG DNA using real-time RT-PCR. The TLR9 inhibitor, chloroquine, suppressed CpG DNA-induced MMP-9 expression and its activity. Moreover, CpG DNA induced the phosphorylation of ERK and the inhibition of ERK by U0126 suppressed CpG DNA-induced MMP-9 expression and its activity. CpG DNA stimulated IkappaB-alpha degradation and luciferase activity. In addition, pretreatment of SN-50, the inhibitor of NFkappaB, strongly blocked the CpG DNA-induced MMP-9 expression and activity. CONCLUSION: These observations suggest that CpG DNA may play important roles in the activation of macrophages by regulating the production of MMP-9 via the sequential TLR9-ERK-NFkappaB signaling pathway.
