Regulation of MMP-9 by a WIN-binding site in the monocyte-macrophage system independent from cannabinoid receptors.
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 (WI...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3491062?pdf=render |
| _version_ | 1819099325492363264 |
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| author | Svantje Tauber Katrin Paulsen Susanne Wolf Peggy Synwoldt Andreas Pahl Regine Schneider-Stock Oliver Ullrich |
| author_facet | Svantje Tauber Katrin Paulsen Susanne Wolf Peggy Synwoldt Andreas Pahl Regine Schneider-Stock Oliver Ullrich |
| author_sort | Svantje Tauber |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-22T00:45:05Z |
| format | Article |
| id | doaj.art-c36678086749466aa10e6683c2dbbc54 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-22T00:45:05Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-c36678086749466aa10e6683c2dbbc542022-12-21T18:44:35ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-01711e4827210.1371/journal.pone.0048272Regulation of MMP-9 by a WIN-binding site in the monocyte-macrophage system independent from cannabinoid receptors.Svantje TauberKatrin PaulsenSusanne WolfPeggy SynwoldtAndreas PahlRegine Schneider-StockOliver UllrichThe 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.http://europepmc.org/articles/PMC3491062?pdf=render |
| spellingShingle | Svantje Tauber Katrin Paulsen Susanne Wolf Peggy Synwoldt Andreas Pahl Regine Schneider-Stock Oliver Ullrich Regulation of MMP-9 by a WIN-binding site in the monocyte-macrophage system independent from cannabinoid receptors. PLoS ONE |
| title | Regulation of MMP-9 by a WIN-binding site in the monocyte-macrophage system independent from cannabinoid receptors. |
| title_full | Regulation of MMP-9 by a WIN-binding site in the monocyte-macrophage system independent from cannabinoid receptors. |
| title_fullStr | Regulation of MMP-9 by a WIN-binding site in the monocyte-macrophage system independent from cannabinoid receptors. |
| title_full_unstemmed | Regulation of MMP-9 by a WIN-binding site in the monocyte-macrophage system independent from cannabinoid receptors. |
| title_short | Regulation of MMP-9 by a WIN-binding site in the monocyte-macrophage system independent from cannabinoid receptors. |
| title_sort | regulation of mmp 9 by a win binding site in the monocyte macrophage system independent from cannabinoid receptors |
| url | http://europepmc.org/articles/PMC3491062?pdf=render |
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