TY - MGZN T1 - Regulation of MMP-9 by a WIN-Binding Site in the Monocyte-Macrophage System Independent from Cannabinoid Receptors T3 - PLoS ONE 7.11 (2012): 15.11.2012 A1 - Tauber,Svantje A1 - Paulsen,Katrin A1 - Wolf,Susanne A1 - Synwoldt,Peggy A1 - Pahl,Andreas A1 - Schneider-Stock,Regine A1 - Ullrich,Oliver Y1 - 2012/11/16 N2 - 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, which subsequently down-regulated MMP-9 mRNA expression via a ERK1/2-phosphorylation-dependent pathway. Surprisingly, the anti-inflammatory effect was independent from classical cannabinoid receptors. Our experiments supposed an involvement of TRPV1, but other yet unidentified sites are also possible. We conclude that cannabinoid-induced control of MMP-9 in the monocyte-macrophage system via a cannabinoid-receptor independent pathway represents a general option for tissue protection during inflammation, such as during lung inflammation and other diseases associated with inflammatory tissue damage. KW - - CY - Erlangen PB - Universitätsbibliothek der Universität Erlangen-Nürnberg AD - Universitätsstraße. 4, 91054 Erlangen L2 - http://www.opus.ub.uni-erlangen.de/opus/volltexte/2012/3885 ER -