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

作者：Lim Eun Jung; Lee Sun Hye; Lee Jin Gu; Kim Jae Ryong; Yun Sung Su; Baek Suk Hwan; Lee ChuHee^*

来源：Experimental and Molecular Medicine, 2007, 39(2): 239-245.

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

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.

• 出版日期2007-4-30