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Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/22486

Title: Synthesis and Validation of a Hydroxypyrone-Based, Potent, and Specific Matrix Metalloproteinase-12 Inhibitor with Anti-Inflammatory Activity In Vitro and In Vivo
Authors: Aerts, J.
Vandenbroucke, R. E.
Dera, R.
Balusu, S.
Van Wonterghem, E.
Moons, L.
Libert, C.
Dehaen, W.
Arckens, L.
Issue Date: 2015
Citation: MEDIATORS OF INFLAMMATION, 2015, (Art N° 510679)
Abstract: A hydroxypyrone-based matrix metalloproteinase (MMP) inhibitor was synthesized and assayed for its inhibitory capacity towards a panel of ten different MMPs. The compound exhibited selective inhibition towards MMP-12. The effects of inhibition of MMP-12 on endotoxemia and inflammation-induced blood-cerebrospinal fluid barrier (BCSFB) disruption were assessed both in vitro and in vivo. Similar to MMP-12 deficient mice, inhibitor-treated mice displayed significantly lower lipopolysaccharide-(LPS-) induced lethality compared to vehicle treated controls. Following LPS injection Mmp-12 mRNA expression was massively upregulated in choroid plexus tissue and a concomitant increase in BCSFB permeability was observed, which was restricted in inhibitor-treated mice. Moreover, an LPS-induced decrease in tight junction permeability of primary choroid plexus epithelial cells was attenuated by inhibitor application in vitro. Taken together, this hydroxypyrone-based inhibitor is selective towards MMP-12 and displays anti-inflammatory activity in vitro and in vivo.
Notes: [Aerts, J.; Arckens, L.] Katholieke Univ Leuven, Lab Neuroplast & Neuroprote, B-3000 Leuven, Belgium. [Vandenbroucke, R. E.; Balusu, S.; Van Wonterghem, E.; Libert, C.] VIB, Inflammat Res Ctr, B-9052 Ghent, Belgium. [Vandenbroucke, R. E.; Balusu, S.; Van Wonterghem, E.; Libert, C.] Univ Ghent, Dept Biomed Mol Biol, B-9052 Ghent, Belgium. [Dera, R.; Dehaen, W.] Katholieke Univ Leuven, Mol Design & Synth, B-3000 Leuven, Belgium. [Dera, R.] UHasselt, Organ & Biopolymer Chem, B-3590 Diepenbeek, Belgium. [Moons, L.] Katholieke Univ Leuven, Lab Neural Circuit Dev & Regenerat, B-3000 Leuven, Belgium.
URI: http://hdl.handle.net/1942/22486
DOI: 10.1155/2015/510679
ISI #: 000360123200001
ISSN: 0962-9351
Category: A1
Type: Journal Contribution
Validation: ecoom, 2016
Appears in Collections: Research publications

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