Exp Mol Med.  2007 Apr;39(2):239-245.

Toll-like receptor 9 dependent activation of MAPK and NF-kB is required for the CpG ODN-induced matrix metalloproteinase-9 expression

• Lim EJ
• Lee SH
• Lee JG
• Kim JR
• Yun SS
• Baek SH
• Lee C

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.

Keyword

CpG-oligonucleotide; extracellular signal-regulated MAP kinases; matrix metalloproteinase 9; NF- kappa B; p38 mitogen-activated protein kinases; Toll-like receptor 9

MeSH Terms

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