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Blocking Interleukin-1β Induces a Healing-Associated Wound Macrophage Phenotype and Improves Healing in Type 2 Diabetes

Diabetes is associated with persistent inflammation and defective tissue repair responses. The hypothesis of this study was that interleukin (IL)-1β is part of a proinflammatory positive feedback loop that sustains a persistent proinflammatory wound macrophage phenotype that contributes to impaired...

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Detalles Bibliográficos
Autores principales: Mirza, Rita E., Fang, Milie M., Ennis, William J., Koh, Timothy J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3712034/
https://www.ncbi.nlm.nih.gov/pubmed/23493576
http://dx.doi.org/10.2337/db12-1450
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author Mirza, Rita E.
Fang, Milie M.
Ennis, William J.
Koh, Timothy J.
author_facet Mirza, Rita E.
Fang, Milie M.
Ennis, William J.
Koh, Timothy J.
author_sort Mirza, Rita E.
collection PubMed
description Diabetes is associated with persistent inflammation and defective tissue repair responses. The hypothesis of this study was that interleukin (IL)-1β is part of a proinflammatory positive feedback loop that sustains a persistent proinflammatory wound macrophage phenotype that contributes to impaired healing in diabetes. Macrophages isolated from wounds in diabetic humans and mice exhibited a proinflammatory phenotype, including expression and secretion of IL-1β. The diabetic wound environment appears to be sufficient to induce these inflammatory phenomena because in vitro studies demonstrated that conditioned medium of both mouse and human wounds upregulates expression of proinflammatory genes and downregulates expression of prohealing factors in cultured macrophages. Furthermore, inhibiting the IL-1β pathway using a neutralizing antibody and macrophages from IL-1 receptor knockout mice blocked the conditioned medium–induced upregulation of proinflammatory genes and downregulation of prohealing factors. Importantly, inhibiting the IL-1β pathway in wounds of diabetic mice using a neutralizing antibody induced a switch from proinflammatory to healing-associated macrophage phenotypes, increased levels of wound growth factors, and improved healing of these wounds. Our findings indicate that targeting the IL-1β pathway represents a new therapeutic approach for improving the healing of diabetic wounds.
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spelling pubmed-37120342014-07-01 Blocking Interleukin-1β Induces a Healing-Associated Wound Macrophage Phenotype and Improves Healing in Type 2 Diabetes Mirza, Rita E. Fang, Milie M. Ennis, William J. Koh, Timothy J. Diabetes Original Research Diabetes is associated with persistent inflammation and defective tissue repair responses. The hypothesis of this study was that interleukin (IL)-1β is part of a proinflammatory positive feedback loop that sustains a persistent proinflammatory wound macrophage phenotype that contributes to impaired healing in diabetes. Macrophages isolated from wounds in diabetic humans and mice exhibited a proinflammatory phenotype, including expression and secretion of IL-1β. The diabetic wound environment appears to be sufficient to induce these inflammatory phenomena because in vitro studies demonstrated that conditioned medium of both mouse and human wounds upregulates expression of proinflammatory genes and downregulates expression of prohealing factors in cultured macrophages. Furthermore, inhibiting the IL-1β pathway using a neutralizing antibody and macrophages from IL-1 receptor knockout mice blocked the conditioned medium–induced upregulation of proinflammatory genes and downregulation of prohealing factors. Importantly, inhibiting the IL-1β pathway in wounds of diabetic mice using a neutralizing antibody induced a switch from proinflammatory to healing-associated macrophage phenotypes, increased levels of wound growth factors, and improved healing of these wounds. Our findings indicate that targeting the IL-1β pathway represents a new therapeutic approach for improving the healing of diabetic wounds. American Diabetes Association 2013-07 2013-06-14 /pmc/articles/PMC3712034/ /pubmed/23493576 http://dx.doi.org/10.2337/db12-1450 Text en © 2013 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.
spellingShingle Original Research
Mirza, Rita E.
Fang, Milie M.
Ennis, William J.
Koh, Timothy J.
Blocking Interleukin-1β Induces a Healing-Associated Wound Macrophage Phenotype and Improves Healing in Type 2 Diabetes
title Blocking Interleukin-1β Induces a Healing-Associated Wound Macrophage Phenotype and Improves Healing in Type 2 Diabetes
title_full Blocking Interleukin-1β Induces a Healing-Associated Wound Macrophage Phenotype and Improves Healing in Type 2 Diabetes
title_fullStr Blocking Interleukin-1β Induces a Healing-Associated Wound Macrophage Phenotype and Improves Healing in Type 2 Diabetes
title_full_unstemmed Blocking Interleukin-1β Induces a Healing-Associated Wound Macrophage Phenotype and Improves Healing in Type 2 Diabetes
title_short Blocking Interleukin-1β Induces a Healing-Associated Wound Macrophage Phenotype and Improves Healing in Type 2 Diabetes
title_sort blocking interleukin-1β induces a healing-associated wound macrophage phenotype and improves healing in type 2 diabetes
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3712034/
https://www.ncbi.nlm.nih.gov/pubmed/23493576
http://dx.doi.org/10.2337/db12-1450
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