Referenced in: none

Automatically associated channels: TRP , TRPV , TRPV1

Title: Regulation of MMP-9 by a WIN-binding site in the monocyte-macrophage system independent from cannabinoid receptors.

Authors: Svantje Tauber, Katrin Paulsen, Susanne Wolf, Peggy Synwoldt, Andreas Pahl, Regine Schneider-Stock, Oliver Ullrich

Journal, date & volume: PLoS ONE, 2012 , 7, e48272

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/23139770

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, 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.