regulation of mmp-9 by a win-binding site in the monocyte-macrophage system independent from cannabinoid receptors监管mmp-9 monocyte-macrophage win-binding网站的系统独立于大麻素受体.pdfVIP

Regulation of MMP-9 by a WIN-Binding Site in the Monocyte-Macrophage System Independent from Cannabinoid Receptors 1,2 1,2 1 3 3 Svantje Tauber , Katrin Paulsen , Susanne Wolf , Peggy Synwoldt , Andreas Pahl , Regine Schneider- Stock4,5, Oliver Ullrich1,2,6,7,8* 1 Institute of Anatomy, Faculty of Medicine, University of Zurich, Zurich, Switzerland, 2 Institute of Immunology, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany, 3 Nycomed Germany Holding GmbH, Konstanz, Germany, 4 Institute of Pathology, Erlangen, Germany, 5 Institute of Pathology, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany, 6 Department of Machine Design, Engineering Design and Product Development, Institute of Mechanical Engineering, Otto-von- Guericke-University Magdeburg, Magdeburg, Germany, 7 Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, Zurich, Switzerland, 8 Neuroscience Center Zurich, University of Zurich and ETH Zurich, Zurich, Switzerland Abstract The cannabinoid system is known to be involved in the regulation of inflammatory processes. Therefore, drugs targeting cannabinoid receptors are considered as candidates for anti-inflammatory and tissue protective therapy. We demonstrated that the prototypical cannabinoid agonist R(+)WIN55,212-2 (WIN) reduced the secretion of matrix metalloproteinase-9 (MMP-9) in a murine model of cigarette-smoke induced lung inflammation. In experiments using primary cells and cell lines of the monocyte-macrophage-system we found that binding of the cannabinoid-receptor agonist WIN to a stereo-selective, specific binding site in cells of the monocyte-macrophage-system induced a significant down-regulation of MMP-9 secretion and disturbance of intracellular processing, w