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Mesenchymal Stem Cells and Formyl Peptide Receptor 2 Activity in Hyperoxia-Induced Lung Injury in Newborn Mice

Formyl peptide receptor (FPR) 2 is known to play a critical role in regulating inflammation, including either the pro-inflammatory or pro-resolving effects. However, its role in neonatal hyperoxia-induced lung injury has not been delineated. In this study, we investigate whether mesenchymal stem cel...

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Autores principales: Kim, Young Eun, Ahn, So Yoon, Sung, Dong Kyung, Chang, Yun Sil, Park, Won Soon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9500980/
https://www.ncbi.nlm.nih.gov/pubmed/36142517
http://dx.doi.org/10.3390/ijms231810604
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author Kim, Young Eun
Ahn, So Yoon
Sung, Dong Kyung
Chang, Yun Sil
Park, Won Soon
author_facet Kim, Young Eun
Ahn, So Yoon
Sung, Dong Kyung
Chang, Yun Sil
Park, Won Soon
author_sort Kim, Young Eun
collection PubMed
description Formyl peptide receptor (FPR) 2 is known to play a critical role in regulating inflammation, including either the pro-inflammatory or pro-resolving effects. However, its role in neonatal hyperoxia-induced lung injury has not been delineated. In this study, we investigate whether mesenchymal stem cells (MSCs) attenuate hyperoxia-induced neonatal lung injury by regulating FPR2 activity. We observed a significant increase in FPR2 levels in alveolar macrophages (RAW264.7 cells) after H(2)O(2)-induced stress, which decreased after MSC treatment. In the H(2)O(2)-induction model, increased levels of inflammatory cytokines (IL-1α and TNF-α) were significantly reduced in RAW264.7 cells after treatment with WRW4, an inhibitor of FPR2, or MSCs. Viability of lung epithelial cells and endothelial cells was significantly improved when cultured in the conditioned media of RAW264.7 cells treated with WRW4 or MSCs, compared to when cultured in the conditioned media of control RAW265.7 cells exposed to H(2)O(2). For the in vivo study, wild-type and FPR2 knockout (FPR2(−/−)) C57/BL6 mouse pups were randomly exposed to 80% oxygen or room air from postnatal day (P) 1 to P14. At P5, 2 × 10(5) MSCs were transplanted intratracheally. MSCs reduced the elevated FPR2 activity at P7 and improved the decreased FPR2 activity as well as the increased immuno-stained FPR2 activity in alveolar macrophages in hyperoxic lungs at P14. Both FPR2(−/−) and MSCs similarly attenuated impaired alveolarization and angiogenesis, and increased apoptosis and inflammation of hyperoxic lungs without synergistic effects. Our findings suggest that the protective effects of MSCs in hyperoxic lung injury might be related to indirect modulation of FPR2 activity, at least of alveolar macrophages in neonatal mice.
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spelling pubmed-95009802022-09-24 Mesenchymal Stem Cells and Formyl Peptide Receptor 2 Activity in Hyperoxia-Induced Lung Injury in Newborn Mice Kim, Young Eun Ahn, So Yoon Sung, Dong Kyung Chang, Yun Sil Park, Won Soon Int J Mol Sci Article Formyl peptide receptor (FPR) 2 is known to play a critical role in regulating inflammation, including either the pro-inflammatory or pro-resolving effects. However, its role in neonatal hyperoxia-induced lung injury has not been delineated. In this study, we investigate whether mesenchymal stem cells (MSCs) attenuate hyperoxia-induced neonatal lung injury by regulating FPR2 activity. We observed a significant increase in FPR2 levels in alveolar macrophages (RAW264.7 cells) after H(2)O(2)-induced stress, which decreased after MSC treatment. In the H(2)O(2)-induction model, increased levels of inflammatory cytokines (IL-1α and TNF-α) were significantly reduced in RAW264.7 cells after treatment with WRW4, an inhibitor of FPR2, or MSCs. Viability of lung epithelial cells and endothelial cells was significantly improved when cultured in the conditioned media of RAW264.7 cells treated with WRW4 or MSCs, compared to when cultured in the conditioned media of control RAW265.7 cells exposed to H(2)O(2). For the in vivo study, wild-type and FPR2 knockout (FPR2(−/−)) C57/BL6 mouse pups were randomly exposed to 80% oxygen or room air from postnatal day (P) 1 to P14. At P5, 2 × 10(5) MSCs were transplanted intratracheally. MSCs reduced the elevated FPR2 activity at P7 and improved the decreased FPR2 activity as well as the increased immuno-stained FPR2 activity in alveolar macrophages in hyperoxic lungs at P14. Both FPR2(−/−) and MSCs similarly attenuated impaired alveolarization and angiogenesis, and increased apoptosis and inflammation of hyperoxic lungs without synergistic effects. Our findings suggest that the protective effects of MSCs in hyperoxic lung injury might be related to indirect modulation of FPR2 activity, at least of alveolar macrophages in neonatal mice. MDPI 2022-09-13 /pmc/articles/PMC9500980/ /pubmed/36142517 http://dx.doi.org/10.3390/ijms231810604 Text en © 2022 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
Kim, Young Eun
Ahn, So Yoon
Sung, Dong Kyung
Chang, Yun Sil
Park, Won Soon
Mesenchymal Stem Cells and Formyl Peptide Receptor 2 Activity in Hyperoxia-Induced Lung Injury in Newborn Mice
title Mesenchymal Stem Cells and Formyl Peptide Receptor 2 Activity in Hyperoxia-Induced Lung Injury in Newborn Mice
title_full Mesenchymal Stem Cells and Formyl Peptide Receptor 2 Activity in Hyperoxia-Induced Lung Injury in Newborn Mice
title_fullStr Mesenchymal Stem Cells and Formyl Peptide Receptor 2 Activity in Hyperoxia-Induced Lung Injury in Newborn Mice
title_full_unstemmed Mesenchymal Stem Cells and Formyl Peptide Receptor 2 Activity in Hyperoxia-Induced Lung Injury in Newborn Mice
title_short Mesenchymal Stem Cells and Formyl Peptide Receptor 2 Activity in Hyperoxia-Induced Lung Injury in Newborn Mice
title_sort mesenchymal stem cells and formyl peptide receptor 2 activity in hyperoxia-induced lung injury in newborn mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9500980/
https://www.ncbi.nlm.nih.gov/pubmed/36142517
http://dx.doi.org/10.3390/ijms231810604
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