Toll-like receptor 9 dependent activation of MAPK and NF-kB is required for the CpG ODN-induced matrix metalloproteinase-9 expression.
- Author:
Eun Jung LIM
1
;
Sun Hye LEE
;
Jin Gu LEE
;
Jae Ryong KIM
;
Sung Su YUN
;
Suk Hwan BAEK
;
ChuHee LEE
Author Information
1. Department of Biochemistry and Molecular Biology, College of Medicine, Yeungnam University, Daegu 705-717, Korea. chlee2@ynu.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
CpG-oligonucleotide;
extracellular signal-regulated MAP kinases;
matrix metalloproteinase 9;
NF- kappa B;
p38 mitogen-activated protein kinases;
Toll-like receptor 9
- MeSH:
Animals;
Cell Line;
Enzyme Activation/drug effects;
Enzyme Induction/drug effects;
Matrix Metalloproteinase 9/*biosynthesis;
Mice;
Mitogen-Activated Protein Kinase 1/antagonists & inhibitors/metabolism;
Mitogen-Activated Protein Kinase 3/antagonists & inhibitors/metabolism;
Mitogen-Activated Protein Kinases/*metabolism;
NF-kappa B/*metabolism;
Oligodeoxyribonucleotides/*pharmacology;
Signal Transduction/drug effects;
Toll-Like Receptor 9/antagonists & inhibitors/*metabolism;
p38 Mitogen-Activated Protein Kinases/antagonists & inhibitors/metabolism
- From:Experimental & Molecular Medicine
2007;39(2):239-245
- CountryRepublic of Korea
- Language:English
-
Abstract:
Unmethylated CpG oligodeoxynucleotides (CpG ODNs) activate immune cells to produce immune mediators. This study demonstrates that in murine macrophage RAW 264.7 cells, CpG ODN-mediated matrix metalloproteinase-9 (MMP-9) expression is regulated at transcriptional level and requires de novo protein synthesis. Inhibition of ERK and p38 MAPK, but not JNK, results in significant decrease of CpG ODN-induced MMP-9 expression. We found that endosomal maturation inhibitors, chloroquine and bafilomycin A, block CpG ODN-induced ERK and p38 MAPK activation and the subsequent MMP-9 expression. We also observed that CpG ODN induces NF-kappa B activation and NF-kappa B is a downstream target of p38 MAPK. Taken together, our data demonstrate that CpG ODN triggers MMP-9 expression via TLR-9 dependent ERK and p38 MAPK activation followed by NF-kappa B activation.
