Nakagami Gojiro, Minematsu Takeo, Morohoshi Tomohiro, Yamane Takumi, Kanazawa Toshiki, Huang Lijuan, Asada Mayumi, Nagase Takashi, Ikeda Shin-ichi, Ikeda Tsukasa, Sanada Hiromi
a Department of Gerontological Nursing/Wound Care Management, Graduate School of Medicine , The University of Tokyo , Tokyo , Japan.
Biosci Biotechnol Biochem. 2015;79(10):1719-24. doi: 10.1080/09168451.2015.1056509. Epub 2015 Jun 22.
Quorum sensing is a cell-to-cell communication mechanism, which is responsible for regulating a number of bacterial virulence factors and biofilm maturation and therefore plays an important role for establishing wound infection. Quorum-sensing signals may induce inflammation and predispose wounds to infection by Pseudomonas aeruginosa; however, the interaction has not been well investigated. We examined the effects of the P. aeruginosa las quorum-sensing signal, N-3-oxo-dodecanoyl homoserine lactone (3OC12-HSL), on matrix metalloproteinase (MMP) 9 expression in Rat-1 fibroblasts. 3OC12-HSL upregulated the expression of the MMP9 gene bearing an activator protein-1 (AP-1) binding site in the promoter region. We further investigated the mechanism underlying this effect. c-Fos gene expression increased rapidly after exposure to 3OC12-HSL, and nuclear translocation of c-Fos protein was observed; both effects were reduced by pretreatment with an AP-1 inhibitor. These results suggest that 3OC12-HSL can alter MMP9 gene expression in fibroblasts via the AP-1 signaling pathway.
群体感应是一种细胞间通讯机制，负责调控多种细菌毒力因子和生物膜成熟，因此在伤口感染的发生中起着重要作用。群体感应信号可能会引发炎症，并使伤口易受铜绿假单胞菌感染；然而，这种相互作用尚未得到充分研究。我们研究了铜绿假单胞菌的las群体感应信号N-3-氧代十二烷酰高丝氨酸内酯（3OC12-HSL）对大鼠1型成纤维细胞中基质金属蛋白酶（MMP）9表达的影响。3OC12-HSL上调了启动子区域带有激活蛋白-1（AP-1）结合位点的MMP9基因的表达。我们进一步研究了这种作用的潜在机制。暴露于3OC12-HSL后，c-Fos基因表达迅速增加，并观察到c-Fos蛋白的核转位；这两种效应均被AP-1抑制剂预处理所减弱。这些结果表明，3OC12-HSL可通过AP-1信号通路改变成纤维细胞中MMP9基因的表达。
