1.Toll-like receptor 9 dependent activation of MAPK and NF-kB is required for the CpG ODN-induced matrix metalloproteinase-9 expression.
Eun Jung LIM ; Sun Hye LEE ; Jin Gu LEE ; Jae Ryong KIM ; Sung Su YUN ; Suk Hwan BAEK ; ChuHee LEE
Experimental & Molecular Medicine 2007;39(2):239-245
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.
Animals
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Cell Line
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Enzyme Activation/drug effects
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Enzyme Induction/drug effects
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Matrix Metalloproteinase 9/*biosynthesis
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Mice
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Mitogen-Activated Protein Kinase 1/antagonists & inhibitors/metabolism
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Mitogen-Activated Protein Kinase 3/antagonists & inhibitors/metabolism
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Mitogen-Activated Protein Kinases/*metabolism
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NF-kappa B/*metabolism
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Oligodeoxyribonucleotides/*pharmacology
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Signal Transduction/drug effects
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Toll-Like Receptor 9/antagonists & inhibitors/*metabolism
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p38 Mitogen-Activated Protein Kinases/antagonists & inhibitors/metabolism