| First Author | Tauber S | Year | 2012 |
| Journal | PLoS One | Volume | 7 |
| Issue | 11 | Pages | e48272 |
| PubMed ID | 23139770 | Mgi Jnum | J:194955 |
| Mgi Id | MGI:5475094 | Doi | 10.1371/journal.pone.0048272 |
| Citation | Tauber S, et al. (2012) Regulation of MMP-9 by a WIN-binding site in the monocyte-macrophage system independent from cannabinoid receptors. PLoS One 7(11):e48272 |
| abstractText | 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. |
