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KMID : 0620920070390020239
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Experimental & Molecular Medicine
2007 Volume.39 No. 2 p.239 ~ p.245
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Toll-like receptor 9 dependent activation of MAPK and NF-kB is required for the CpG ODN-induced matrix metalloproteinase-9 expression
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Lim Eun-Jung
Lee Sun-Hye
Lee Jin-Gu
Kim Jae-Ryong
Yun Sung-Soo
Baek Suk-Hwan
Lee Chu-Hee
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Abstract
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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-kB activation and NF-kB 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-kB activation.
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KEYWORD
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CpG-oligonucleotide, extracellular signal-regulated MAP kinases, matrix metalloproteinase 9, NF- kappa B, p38 mitogen-activated protein kinases, Toll-like receptor 9
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