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Immuno-modulatory effect of local rhEGF treatment during tissue repair in diabetic ulcers

Wound healing is a complex process that can be severely impaired due to pathological situations such as diabetes mellitus. Diabetic foot ulcers are a common complication of this pathology and are characterized by an excessive inflammatory response. In this work, the effects of local treatment with r...

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Autores principales: García-Honduvilla, Natalio, Cifuentes, Alberto, Ortega, Miguel A, Pastor, Marta, Gainza, Garazi, Gainza, Eusebio, Buján, Julia, Álvarez-Mon, Melchor
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Bioscientifica Ltd 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5900456/
https://www.ncbi.nlm.nih.gov/pubmed/29592858
http://dx.doi.org/10.1530/EC-18-0117
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author García-Honduvilla, Natalio
Cifuentes, Alberto
Ortega, Miguel A
Pastor, Marta
Gainza, Garazi
Gainza, Eusebio
Buján, Julia
Álvarez-Mon, Melchor
author_facet García-Honduvilla, Natalio
Cifuentes, Alberto
Ortega, Miguel A
Pastor, Marta
Gainza, Garazi
Gainza, Eusebio
Buján, Julia
Álvarez-Mon, Melchor
author_sort García-Honduvilla, Natalio
collection PubMed
description Wound healing is a complex process that can be severely impaired due to pathological situations such as diabetes mellitus. Diabetic foot ulcers are a common complication of this pathology and are characterized by an excessive inflammatory response. In this work, the effects of local treatment with recombinant human epidermal growth factor (rhEGF) were studied using a full-thickness wound healing model in streptozotocin-induced diabetic rats. Wound healing process was assessed with different concentrations of rhEGF (0.1, 0.5, 2.0 and 8.0 µg/mL), placebo and both diabetic and non-diabetic controls (n = 53). The macroscopic healing observed in treated diabetic rats was affected by rhEGF concentration. Histologically, we also observed an improvement in the epithelialization, granulation tissue formation and maturation in treated groups, finding again the best response at doses of 0.5 and 2.0 µg/mL. Afterwards, the tissue immune response over time was assessed in diabetic rats using the most effective concentrations of rhEGF (0.5 and 2.0 µg/mL), compared to controls. The presence of macrophages, CD4(+) T lymphocytes and CD8(+) T lymphocytes, in the reparative tissue was quantified, and cytokine expression was measured by quantitative real-time PCR. rhEGF treatment caused a reduction in the number of infiltrating macrophages in the healing tissue of diabetic, as well as diminished activation of these leukocytes. These findings show that local administration of rhEGF improves the healing process of excisional wounds and the quality of the neoformed tissue in a dose-dependent manner. Besides, this treatment reduces the local inflammation associated with diabetic healing, indicating immuno-modulatory properties.
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spelling pubmed-59004562018-04-19 Immuno-modulatory effect of local rhEGF treatment during tissue repair in diabetic ulcers García-Honduvilla, Natalio Cifuentes, Alberto Ortega, Miguel A Pastor, Marta Gainza, Garazi Gainza, Eusebio Buján, Julia Álvarez-Mon, Melchor Endocr Connect Research Wound healing is a complex process that can be severely impaired due to pathological situations such as diabetes mellitus. Diabetic foot ulcers are a common complication of this pathology and are characterized by an excessive inflammatory response. In this work, the effects of local treatment with recombinant human epidermal growth factor (rhEGF) were studied using a full-thickness wound healing model in streptozotocin-induced diabetic rats. Wound healing process was assessed with different concentrations of rhEGF (0.1, 0.5, 2.0 and 8.0 µg/mL), placebo and both diabetic and non-diabetic controls (n = 53). The macroscopic healing observed in treated diabetic rats was affected by rhEGF concentration. Histologically, we also observed an improvement in the epithelialization, granulation tissue formation and maturation in treated groups, finding again the best response at doses of 0.5 and 2.0 µg/mL. Afterwards, the tissue immune response over time was assessed in diabetic rats using the most effective concentrations of rhEGF (0.5 and 2.0 µg/mL), compared to controls. The presence of macrophages, CD4(+) T lymphocytes and CD8(+) T lymphocytes, in the reparative tissue was quantified, and cytokine expression was measured by quantitative real-time PCR. rhEGF treatment caused a reduction in the number of infiltrating macrophages in the healing tissue of diabetic, as well as diminished activation of these leukocytes. These findings show that local administration of rhEGF improves the healing process of excisional wounds and the quality of the neoformed tissue in a dose-dependent manner. Besides, this treatment reduces the local inflammation associated with diabetic healing, indicating immuno-modulatory properties. Bioscientifica Ltd 2018-03-28 /pmc/articles/PMC5900456/ /pubmed/29592858 http://dx.doi.org/10.1530/EC-18-0117 Text en © 2018 The authors http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research
García-Honduvilla, Natalio
Cifuentes, Alberto
Ortega, Miguel A
Pastor, Marta
Gainza, Garazi
Gainza, Eusebio
Buján, Julia
Álvarez-Mon, Melchor
Immuno-modulatory effect of local rhEGF treatment during tissue repair in diabetic ulcers
title Immuno-modulatory effect of local rhEGF treatment during tissue repair in diabetic ulcers
title_full Immuno-modulatory effect of local rhEGF treatment during tissue repair in diabetic ulcers
title_fullStr Immuno-modulatory effect of local rhEGF treatment during tissue repair in diabetic ulcers
title_full_unstemmed Immuno-modulatory effect of local rhEGF treatment during tissue repair in diabetic ulcers
title_short Immuno-modulatory effect of local rhEGF treatment during tissue repair in diabetic ulcers
title_sort immuno-modulatory effect of local rhegf treatment during tissue repair in diabetic ulcers
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5900456/
https://www.ncbi.nlm.nih.gov/pubmed/29592858
http://dx.doi.org/10.1530/EC-18-0117
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