CCR5 signaling promotes lipopolysaccharide-induced macrophage recruitment and alveolar developmental arrest

The pathogenesis of bronchopulmonary dysplasia (BPD), involves inflammatory, mechanisms that are not fully characterized. Here we report that overexpression of C-C chemokine receptor 5 (CCR5) and its ligands is associated with BPD development. Lipopolysaccharide-induced BPD rats have increased CCR5...

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Autores principales: Chen, Ze, Xie, Xiaohua, Jiang, Na, Li, Jianhui, Shen, Lei, Zhang, Yongjun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7883330/
https://www.ncbi.nlm.nih.gov/pubmed/33589608
http://dx.doi.org/10.1038/s41419-021-03464-7
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author Chen, Ze
Xie, Xiaohua
Jiang, Na
Li, Jianhui
Shen, Lei
Zhang, Yongjun
author_facet Chen, Ze
Xie, Xiaohua
Jiang, Na
Li, Jianhui
Shen, Lei
Zhang, Yongjun
author_sort Chen, Ze
collection PubMed
description The pathogenesis of bronchopulmonary dysplasia (BPD), involves inflammatory, mechanisms that are not fully characterized. Here we report that overexpression of C-C chemokine receptor 5 (CCR5) and its ligands is associated with BPD development. Lipopolysaccharide-induced BPD rats have increased CCR5 and interleukin-1β (IL-1β) levels, and decreased alveolarization, while CCR5 or IL-1β receptor antagonist treatments decreased inflammation and increased alveolarization. CCR5 enhances macrophage migration, macrophage infiltration in the lungs, IL-1β levels, lysyl oxidase activity, and alveolar development arrest. CCR5 expression on monocytes, and its ligands in blood samples from BPD infants, are elevated. Furthermore, batyl alcohol supplementation reduced CCR5 expression and IL-1β production in lipopolysaccharide-exposed rat lungs. Moreover, receptor-interacting kinase 3 (RIP3) upstream regulator of CCR5-cultured RIP3(−/−) macrophages exhibited partly blocked lipopolysaccharide-induced CCR5 expression. We conclude that increased CCR5 expression is a key mechanism in BPD development and represents a novel therapeutic target for treatment.
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spelling pubmed-78833302021-02-16 CCR5 signaling promotes lipopolysaccharide-induced macrophage recruitment and alveolar developmental arrest Chen, Ze Xie, Xiaohua Jiang, Na Li, Jianhui Shen, Lei Zhang, Yongjun Cell Death Dis Article The pathogenesis of bronchopulmonary dysplasia (BPD), involves inflammatory, mechanisms that are not fully characterized. Here we report that overexpression of C-C chemokine receptor 5 (CCR5) and its ligands is associated with BPD development. Lipopolysaccharide-induced BPD rats have increased CCR5 and interleukin-1β (IL-1β) levels, and decreased alveolarization, while CCR5 or IL-1β receptor antagonist treatments decreased inflammation and increased alveolarization. CCR5 enhances macrophage migration, macrophage infiltration in the lungs, IL-1β levels, lysyl oxidase activity, and alveolar development arrest. CCR5 expression on monocytes, and its ligands in blood samples from BPD infants, are elevated. Furthermore, batyl alcohol supplementation reduced CCR5 expression and IL-1β production in lipopolysaccharide-exposed rat lungs. Moreover, receptor-interacting kinase 3 (RIP3) upstream regulator of CCR5-cultured RIP3(−/−) macrophages exhibited partly blocked lipopolysaccharide-induced CCR5 expression. We conclude that increased CCR5 expression is a key mechanism in BPD development and represents a novel therapeutic target for treatment. Nature Publishing Group UK 2021-02-15 /pmc/articles/PMC7883330/ /pubmed/33589608 http://dx.doi.org/10.1038/s41419-021-03464-7 Text en © The Author(s) 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Chen, Ze
Xie, Xiaohua
Jiang, Na
Li, Jianhui
Shen, Lei
Zhang, Yongjun
CCR5 signaling promotes lipopolysaccharide-induced macrophage recruitment and alveolar developmental arrest
title CCR5 signaling promotes lipopolysaccharide-induced macrophage recruitment and alveolar developmental arrest
title_full CCR5 signaling promotes lipopolysaccharide-induced macrophage recruitment and alveolar developmental arrest
title_fullStr CCR5 signaling promotes lipopolysaccharide-induced macrophage recruitment and alveolar developmental arrest
title_full_unstemmed CCR5 signaling promotes lipopolysaccharide-induced macrophage recruitment and alveolar developmental arrest
title_short CCR5 signaling promotes lipopolysaccharide-induced macrophage recruitment and alveolar developmental arrest
title_sort ccr5 signaling promotes lipopolysaccharide-induced macrophage recruitment and alveolar developmental arrest
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7883330/
https://www.ncbi.nlm.nih.gov/pubmed/33589608
http://dx.doi.org/10.1038/s41419-021-03464-7
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