Synthesis and Validation of a Hydroxypyrone-Based, Potent, and Specific Matrix Metalloproteinase-12 Inhibitor with Anti-Inflammatory Activity In Vitro and In Vivo
Joint Authors
Libert, Claude
Vandenbroucke, Roosmarijn E.
Moons, Lieve
Aerts, J.
Dera, R.
Balusu, S.
Van Wonterghem, E.
Dehaen, W.
Arckens, L.
Source
Issue
Vol. 2015, Issue 2015 (31 Dec. 2015), pp.1-9, 9 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2015-08-13
Country of Publication
Egypt
No. of Pages
9
Main Subjects
Abstract EN
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.
American Psychological Association (APA)
Aerts, J.& Vandenbroucke, Roosmarijn E.& Dera, R.& Balusu, S.& Van Wonterghem, E.& Moons, Lieve…[et al.]. 2015. Synthesis and Validation of a Hydroxypyrone-Based, Potent, and Specific Matrix Metalloproteinase-12 Inhibitor with Anti-Inflammatory Activity In Vitro and In Vivo. Mediators of Inflammation،Vol. 2015, no. 2015, pp.1-9.
https://search.emarefa.net/detail/BIM-1072395
Modern Language Association (MLA)
Aerts, J.…[et al.]. Synthesis and Validation of a Hydroxypyrone-Based, Potent, and Specific Matrix Metalloproteinase-12 Inhibitor with Anti-Inflammatory Activity In Vitro and In Vivo. Mediators of Inflammation No. 2015 (2015), pp.1-9.
https://search.emarefa.net/detail/BIM-1072395
American Medical Association (AMA)
Aerts, J.& Vandenbroucke, Roosmarijn E.& Dera, R.& Balusu, S.& Van Wonterghem, E.& Moons, Lieve…[et al.]. Synthesis and Validation of a Hydroxypyrone-Based, Potent, and Specific Matrix Metalloproteinase-12 Inhibitor with Anti-Inflammatory Activity In Vitro and In Vivo. Mediators of Inflammation. 2015. Vol. 2015, no. 2015, pp.1-9.
https://search.emarefa.net/detail/BIM-1072395
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1072395
