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The Small Molecule NLRP3 Inflammasome Inhibitor MCC950 Does Not Alter Wound Healing in Obese Mice

The incidence of chronic wounds is escalating, and the associated healing process is especially problematic in an aging population with increased morbidity. Targeting increased inflammation in chronic wounds is a promising but challenging therapeutic strategy. Indeed, inflammation and especially mac...

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Detalles Bibliográficos
Autores principales: Lee, James S., Robertson, Avril A. B., Cooper, Matthew A., Khosrotehrani, Kiarash
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6274704/
https://www.ncbi.nlm.nih.gov/pubmed/30360489
http://dx.doi.org/10.3390/ijms19113289
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author Lee, James S.
Robertson, Avril A. B.
Cooper, Matthew A.
Khosrotehrani, Kiarash
author_facet Lee, James S.
Robertson, Avril A. B.
Cooper, Matthew A.
Khosrotehrani, Kiarash
author_sort Lee, James S.
collection PubMed
description The incidence of chronic wounds is escalating, and the associated healing process is especially problematic in an aging population with increased morbidity. Targeting increased inflammation in chronic wounds is a promising but challenging therapeutic strategy. Indeed, inflammation and especially macrophages are required for wound healing. As the NLRP3 inflammasome has been implicated with various other inflammatory diseases, in this study, we used MCC950—a selective NLRP3 small molecule inhibitor—on murine models of both acute and chronic wounds. This molecule, while tested for other inflammatory conditions, has never been investigated to reduce topical inflammation driving chronic wounds. We found that there were no significant differences when the treatment was applied either topically or orally in wild-type C57Bl/6 mice and that it even impaired wound healing in obese mice. The treatment was also unable to improve re-epithelialisation or angiogenesis, which are both required for the closure of wounds. We are inclined to believe that MCC950 may inhibit the closure of chronic wounds and that it does not alter wound-associated macrophage polarisation.
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spelling pubmed-62747042018-12-15 The Small Molecule NLRP3 Inflammasome Inhibitor MCC950 Does Not Alter Wound Healing in Obese Mice Lee, James S. Robertson, Avril A. B. Cooper, Matthew A. Khosrotehrani, Kiarash Int J Mol Sci Communication The incidence of chronic wounds is escalating, and the associated healing process is especially problematic in an aging population with increased morbidity. Targeting increased inflammation in chronic wounds is a promising but challenging therapeutic strategy. Indeed, inflammation and especially macrophages are required for wound healing. As the NLRP3 inflammasome has been implicated with various other inflammatory diseases, in this study, we used MCC950—a selective NLRP3 small molecule inhibitor—on murine models of both acute and chronic wounds. This molecule, while tested for other inflammatory conditions, has never been investigated to reduce topical inflammation driving chronic wounds. We found that there were no significant differences when the treatment was applied either topically or orally in wild-type C57Bl/6 mice and that it even impaired wound healing in obese mice. The treatment was also unable to improve re-epithelialisation or angiogenesis, which are both required for the closure of wounds. We are inclined to believe that MCC950 may inhibit the closure of chronic wounds and that it does not alter wound-associated macrophage polarisation. MDPI 2018-10-23 /pmc/articles/PMC6274704/ /pubmed/30360489 http://dx.doi.org/10.3390/ijms19113289 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Communication
Lee, James S.
Robertson, Avril A. B.
Cooper, Matthew A.
Khosrotehrani, Kiarash
The Small Molecule NLRP3 Inflammasome Inhibitor MCC950 Does Not Alter Wound Healing in Obese Mice
title The Small Molecule NLRP3 Inflammasome Inhibitor MCC950 Does Not Alter Wound Healing in Obese Mice
title_full The Small Molecule NLRP3 Inflammasome Inhibitor MCC950 Does Not Alter Wound Healing in Obese Mice
title_fullStr The Small Molecule NLRP3 Inflammasome Inhibitor MCC950 Does Not Alter Wound Healing in Obese Mice
title_full_unstemmed The Small Molecule NLRP3 Inflammasome Inhibitor MCC950 Does Not Alter Wound Healing in Obese Mice
title_short The Small Molecule NLRP3 Inflammasome Inhibitor MCC950 Does Not Alter Wound Healing in Obese Mice
title_sort small molecule nlrp3 inflammasome inhibitor mcc950 does not alter wound healing in obese mice
topic Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6274704/
https://www.ncbi.nlm.nih.gov/pubmed/30360489
http://dx.doi.org/10.3390/ijms19113289
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