Journal of the Korean Association of Oral and Maxillofacial Surgeons

The Korean Association of Oral and Maxillofacial Surgeons (대한구강악안면외과학회)
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ROLE OF NF${\kappa}B$ IN TOLL-LIKE RECEPTOR 9-MEDIATED MATRIX METALLOPROTEINASE-9 EXPRESSION

Toll-like receptor 9-매개에 의한 matrix metalloproteinase-9 발현에서 NF${\kappa}B$의 역할

  • Lee, Sang-Hoon (Department of Dentistry, College of Medicine, Yeungnam University) ;
  • Chin, Byung-Rho (Department of Dentistry, College of Medicine, Yeungnam University) ;
  • Baek, Suk-Hwan (Department of Biochemistry & Molecular Biology, College of Medicine, Yeungnam University)
  • 이상훈 (영남대학교 의과대학 치과학교실) ;
  • 진병로 (영남대학교 의과대학 치과학교실) ;
  • 백석환 (영남대학교 의과대학 생화학.분자생물학교실)
  • Published : 2007.12.31
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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). Methods and materials: Macrophages were cultured in the presence of 10% 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 NF${\kappa}B$ activation, and luciferase promoter assay was for the NF${\kappa}B$ 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 $I{\kappa}B-{\alpha}$ degradation and luciferase activity. In addition, pretreatment of SN-50, the inhibitor of NF${\kappa}B$, 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-NF${\kappa}B$ signaling pathway.

Keywords

References

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