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The Influence of Apremilast-Induced Macrophage Polarization on Intestinal Wound Healing
There is compelling evidence suggesting a pivotal role played by macrophages in orchestrating intestinal wound healing. Since macrophages display significant plasticity and heterogeneity, exhibiting an either classically activated (M1-like) or alternatively activated (M2-like) phenotype, they can ag...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10219563/ https://www.ncbi.nlm.nih.gov/pubmed/37240465 http://dx.doi.org/10.3390/jcm12103359 |
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author | Mohr, Annika Besser, Manuela Broichhausen, Sonja Winter, Maximiliane Bungert, Alexander D. Strücker, Benjamin Juratli, Mazen A. Pascher, Andreas Becker, Felix |
author_facet | Mohr, Annika Besser, Manuela Broichhausen, Sonja Winter, Maximiliane Bungert, Alexander D. Strücker, Benjamin Juratli, Mazen A. Pascher, Andreas Becker, Felix |
author_sort | Mohr, Annika |
collection | PubMed |
description | There is compelling evidence suggesting a pivotal role played by macrophages in orchestrating intestinal wound healing. Since macrophages display significant plasticity and heterogeneity, exhibiting an either classically activated (M1-like) or alternatively activated (M2-like) phenotype, they can aggravate or attenuate intestinal wound healing. Growing evidence also demonstrates a causal link between impaired mucosal healing in inflammatory bowel disease (IBD) and defects in the polarization of pro-resolving macrophages. By targeting the switch from M1 to M2 macrophages, the phosphodiesterase-4 inhibitor Apremilast has gained recent attention as a potential IBD drug. However, there is a gap in our current knowledge regarding the impact of Apremilast-induced macrophages’ polarization on intestinal wound healing. The THP-1 cells were differentiated and polarized into M1 and M2 macrophages, and subsequently treated with Apremilast. Gene expression analysis was performed to characterize macrophage M1 and M2 phenotypes, and to identify possible target genes of Apremilast and the involved pathways. Next, intestinal fibroblast (CCD-18) and epithelial (CaCo-2) cell lines were scratch-wounded and exposed to a conditioned medium of Apremilast-treated macrophages. Apremilast had a clear effect on macrophage polarization, inducing an M1 to M2 phenotype switch, which was associated with NF-κB signaling. In addition, the wound-healing assays revealed an indirect influence of Apremilast on fibroblast migration. Our results support the hypothesis of Apremilast acting through the NF-κB-pathway and provide new insights into the interaction with fibroblast during intestinal wound healing. |
format | Online Article Text |
id | pubmed-10219563 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-102195632023-05-27 The Influence of Apremilast-Induced Macrophage Polarization on Intestinal Wound Healing Mohr, Annika Besser, Manuela Broichhausen, Sonja Winter, Maximiliane Bungert, Alexander D. Strücker, Benjamin Juratli, Mazen A. Pascher, Andreas Becker, Felix J Clin Med Article There is compelling evidence suggesting a pivotal role played by macrophages in orchestrating intestinal wound healing. Since macrophages display significant plasticity and heterogeneity, exhibiting an either classically activated (M1-like) or alternatively activated (M2-like) phenotype, they can aggravate or attenuate intestinal wound healing. Growing evidence also demonstrates a causal link between impaired mucosal healing in inflammatory bowel disease (IBD) and defects in the polarization of pro-resolving macrophages. By targeting the switch from M1 to M2 macrophages, the phosphodiesterase-4 inhibitor Apremilast has gained recent attention as a potential IBD drug. However, there is a gap in our current knowledge regarding the impact of Apremilast-induced macrophages’ polarization on intestinal wound healing. The THP-1 cells were differentiated and polarized into M1 and M2 macrophages, and subsequently treated with Apremilast. Gene expression analysis was performed to characterize macrophage M1 and M2 phenotypes, and to identify possible target genes of Apremilast and the involved pathways. Next, intestinal fibroblast (CCD-18) and epithelial (CaCo-2) cell lines were scratch-wounded and exposed to a conditioned medium of Apremilast-treated macrophages. Apremilast had a clear effect on macrophage polarization, inducing an M1 to M2 phenotype switch, which was associated with NF-κB signaling. In addition, the wound-healing assays revealed an indirect influence of Apremilast on fibroblast migration. Our results support the hypothesis of Apremilast acting through the NF-κB-pathway and provide new insights into the interaction with fibroblast during intestinal wound healing. MDPI 2023-05-09 /pmc/articles/PMC10219563/ /pubmed/37240465 http://dx.doi.org/10.3390/jcm12103359 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Mohr, Annika Besser, Manuela Broichhausen, Sonja Winter, Maximiliane Bungert, Alexander D. Strücker, Benjamin Juratli, Mazen A. Pascher, Andreas Becker, Felix The Influence of Apremilast-Induced Macrophage Polarization on Intestinal Wound Healing |
title | The Influence of Apremilast-Induced Macrophage Polarization on Intestinal Wound Healing |
title_full | The Influence of Apremilast-Induced Macrophage Polarization on Intestinal Wound Healing |
title_fullStr | The Influence of Apremilast-Induced Macrophage Polarization on Intestinal Wound Healing |
title_full_unstemmed | The Influence of Apremilast-Induced Macrophage Polarization on Intestinal Wound Healing |
title_short | The Influence of Apremilast-Induced Macrophage Polarization on Intestinal Wound Healing |
title_sort | influence of apremilast-induced macrophage polarization on intestinal wound healing |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10219563/ https://www.ncbi.nlm.nih.gov/pubmed/37240465 http://dx.doi.org/10.3390/jcm12103359 |
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