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Alveolar Epithelial Cells Promote IGF-1 Production by Alveolar Macrophages Through TGF-β to Suppress Endogenous Inflammatory Signals

To maintain alveolar gas exchange, the alveolar surface has to limit unnecessary inflammatory responses. This involves crosstalk between alveolar epithelial cells (AECs) and alveolar macrophages (AMs) in response to damaging factors. We recently showed that insulin-like growth factor (IGF)-1 regulat...

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Autores principales: Mu, Mimi, Gao, Peiyu, Yang, Qian, He, Jing, Wu, Fengjiao, Han, Xue, Guo, Shujun, Qian, Zhongqing, Song, Chuanwang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7385185/
https://www.ncbi.nlm.nih.gov/pubmed/32793225
http://dx.doi.org/10.3389/fimmu.2020.01585
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author Mu, Mimi
Gao, Peiyu
Yang, Qian
He, Jing
Wu, Fengjiao
Han, Xue
Guo, Shujun
Qian, Zhongqing
Song, Chuanwang
author_facet Mu, Mimi
Gao, Peiyu
Yang, Qian
He, Jing
Wu, Fengjiao
Han, Xue
Guo, Shujun
Qian, Zhongqing
Song, Chuanwang
author_sort Mu, Mimi
collection PubMed
description To maintain alveolar gas exchange, the alveolar surface has to limit unnecessary inflammatory responses. This involves crosstalk between alveolar epithelial cells (AECs) and alveolar macrophages (AMs) in response to damaging factors. We recently showed that insulin-like growth factor (IGF)-1 regulates the phagocytosis of AECs. AMs secrete IGF-1 into the bronchoalveolar lavage fluid (BALF) in response to inflammatory stimuli. However, whether AECs regulate the production of IGF-1 by AMs in response to inflammatory signals remains unclear, as well as the role of IGF-1 in controlling the alveolar balance in the crosstalk between AMs and AECs under inflammatory conditions. In this study, we demonstrated that IGF-1 was upregulated in BALF and lung tissues of acute lung injury (ALI) mice, and that the increased IGF-1 was mainly derived from AMs. In vitro experiments showed that the production and secretion of IGF-1 by AMs as well as the expression of TGF-β were increased in LPS-stimulated AEC-conditioned medium (AEC-CM). Pharmacological blocking of TGF-β in AECs and addition of TGF-β neutralizing antibody to AEC-CM suggested that this AEC-derived cytokine mediates the increased production and secretion of IGF-1 from AMs. Blocking TGF-β synthesis or treatment with TGF-β neutralizing antibody attenuated the increase of IGF-1 in BALF in ALI mice. TGF-β induced the production of IGF-1 by AMs through the PI3K/Akt signaling pathway. IGF-1 prevented LPS-induced p38 MAPK activation and the expression of the inflammatory factors MCP-1, TNF-α, and IL-1β in AECs. However, IGF-1 upregulated PPARγ to increase the phagocytosis of apoptotic cells by AECs. Intratracheal instillation of IGF-1 decreased the number of polymorphonuclear neutrophils in BALF of ALI model mice, reduced alveolar congestion and edema, and suppressed inflammatory cell infiltration in lung tissues. These results elucidated a mechanism by which AECs used TGF-β to regulate IGF-1 production from AMs to attenuate endogenous inflammatory signals during alveolar inflammation.
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spelling pubmed-73851852020-08-12 Alveolar Epithelial Cells Promote IGF-1 Production by Alveolar Macrophages Through TGF-β to Suppress Endogenous Inflammatory Signals Mu, Mimi Gao, Peiyu Yang, Qian He, Jing Wu, Fengjiao Han, Xue Guo, Shujun Qian, Zhongqing Song, Chuanwang Front Immunol Immunology To maintain alveolar gas exchange, the alveolar surface has to limit unnecessary inflammatory responses. This involves crosstalk between alveolar epithelial cells (AECs) and alveolar macrophages (AMs) in response to damaging factors. We recently showed that insulin-like growth factor (IGF)-1 regulates the phagocytosis of AECs. AMs secrete IGF-1 into the bronchoalveolar lavage fluid (BALF) in response to inflammatory stimuli. However, whether AECs regulate the production of IGF-1 by AMs in response to inflammatory signals remains unclear, as well as the role of IGF-1 in controlling the alveolar balance in the crosstalk between AMs and AECs under inflammatory conditions. In this study, we demonstrated that IGF-1 was upregulated in BALF and lung tissues of acute lung injury (ALI) mice, and that the increased IGF-1 was mainly derived from AMs. In vitro experiments showed that the production and secretion of IGF-1 by AMs as well as the expression of TGF-β were increased in LPS-stimulated AEC-conditioned medium (AEC-CM). Pharmacological blocking of TGF-β in AECs and addition of TGF-β neutralizing antibody to AEC-CM suggested that this AEC-derived cytokine mediates the increased production and secretion of IGF-1 from AMs. Blocking TGF-β synthesis or treatment with TGF-β neutralizing antibody attenuated the increase of IGF-1 in BALF in ALI mice. TGF-β induced the production of IGF-1 by AMs through the PI3K/Akt signaling pathway. IGF-1 prevented LPS-induced p38 MAPK activation and the expression of the inflammatory factors MCP-1, TNF-α, and IL-1β in AECs. However, IGF-1 upregulated PPARγ to increase the phagocytosis of apoptotic cells by AECs. Intratracheal instillation of IGF-1 decreased the number of polymorphonuclear neutrophils in BALF of ALI model mice, reduced alveolar congestion and edema, and suppressed inflammatory cell infiltration in lung tissues. These results elucidated a mechanism by which AECs used TGF-β to regulate IGF-1 production from AMs to attenuate endogenous inflammatory signals during alveolar inflammation. Frontiers Media S.A. 2020-07-21 /pmc/articles/PMC7385185/ /pubmed/32793225 http://dx.doi.org/10.3389/fimmu.2020.01585 Text en Copyright © 2020 Mu, Gao, Yang, He, Wu, Han, Guo, Qian and Song. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Mu, Mimi
Gao, Peiyu
Yang, Qian
He, Jing
Wu, Fengjiao
Han, Xue
Guo, Shujun
Qian, Zhongqing
Song, Chuanwang
Alveolar Epithelial Cells Promote IGF-1 Production by Alveolar Macrophages Through TGF-β to Suppress Endogenous Inflammatory Signals
title Alveolar Epithelial Cells Promote IGF-1 Production by Alveolar Macrophages Through TGF-β to Suppress Endogenous Inflammatory Signals
title_full Alveolar Epithelial Cells Promote IGF-1 Production by Alveolar Macrophages Through TGF-β to Suppress Endogenous Inflammatory Signals
title_fullStr Alveolar Epithelial Cells Promote IGF-1 Production by Alveolar Macrophages Through TGF-β to Suppress Endogenous Inflammatory Signals
title_full_unstemmed Alveolar Epithelial Cells Promote IGF-1 Production by Alveolar Macrophages Through TGF-β to Suppress Endogenous Inflammatory Signals
title_short Alveolar Epithelial Cells Promote IGF-1 Production by Alveolar Macrophages Through TGF-β to Suppress Endogenous Inflammatory Signals
title_sort alveolar epithelial cells promote igf-1 production by alveolar macrophages through tgf-β to suppress endogenous inflammatory signals
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7385185/
https://www.ncbi.nlm.nih.gov/pubmed/32793225
http://dx.doi.org/10.3389/fimmu.2020.01585
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