Lim Eun-Jung, Lee Sun-Hye, Lee Jin-Gu, Kim Jae-Ryong, Yun Sung-Su, Baek Suk-Hwan, Lee ChuHee
Department of Biochemistry and Molecular Biology, College of Medicine, Yeungnam University, Daegu 705-717, Korea.
Exp Mol Med. 2007 Apr 30;39(2):239-45. doi: 10.1038/emm.2007.27.
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-kappaB activation and NF-kappaB 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-kappaB activation.
未甲基化的CpG寡脱氧核苷酸（CpG ODNs）可激活免疫细胞以产生免疫介质。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控，且需要从头合成蛋白质。抑制ERK和p38 MAPK，但不抑制JNK，会导致CpG ODN诱导的MMP-9表达显著降低。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可诱导NF-κB激活，且NF-κB是p38 MAPK的下游靶点。综上所述，我们的数据表明，CpG ODN通过依赖TLR-9的ERK和p38 MAPK激活，随后激活NF-κB来触发MMP-9表达。
