Toll-like receptor 9 dependent activation of MAPK and NF-κB is required for the CpG ODN-induced matrix metalloproteinase-9 expression
Toll-like receptor 9 dependent activation of MAPK and NF-κB is required for the CpG ODN-induced matrix metalloproteinase-9 expression
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DOI：
10.1038/emm.2007.27
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发表时间：
2007-04-30
影响因子：
12.8
通讯作者：
Lee, ChuHee
中科院分区：
文献类型：
--
作者：
Lim, Eun-Jung;Lee, Sun-Hye;Lee, ChuHee
未甲基化的 CpG 寡脱氧核苷酸 (CpG ODN) 激活免疫细胞产生免疫介质。本研究表明，在小鼠巨噬细胞 RAW 264.7 细胞中，CpG ODN 介导的基质金属蛋白酶 9 (MMP-9) 表达在转录水平受到调节，并且需要从头合成蛋白质。抑制 ERK 和 p38 MAPK（而非 JNK）会导致 CpG ODN 诱导的 MMP-9 表达显着降低。我们发现内体成熟抑制剂氯喹和巴弗洛霉素 A 可阻断 CpG ODN 诱导的 ERK 和 p38 MAPK 激活以及随后的 MMP-9 表达。我们还观察到 CpG ODN 诱导 NF-kappa B 激活，并且 NF-kappa B 是 p38 MAPK 的下游靶标。综上所述，我们的数据表明，CpG ODN 通过 TLR-9 依赖性 ERK 和 p38 MAPK 激活以及随后的 NF-kappa B 激活来触发 MMP-9 表达。
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.