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A Biodegradable Mg-Based Alloy Inhibited the Inflammatory Response of THP-1 Cell-Derived Macrophages Through the TRPM7–PI3K–AKT1 Signaling Axis

Mg-based alloys might be ideal biomaterials in clinical applications owing to favorable mechanical properties, biodegradability, biocompatibility, and especially their anti-inflammatory properties. However, the precise signaling mechanism underlying the inhibition of inflammation by Mg-based alloys...

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Autores principales: Jin, Liang, Chen, Chenxin, Li, Yutong, Yuan, Feng, Gong, Ruolan, Wu, Jing, Zhang, Hua, Kang, Bin, Yuan, Guangyin, Zeng, Hui, Chen, Tongxin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6902094/
https://www.ncbi.nlm.nih.gov/pubmed/31849975
http://dx.doi.org/10.3389/fimmu.2019.02798
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author Jin, Liang
Chen, Chenxin
Li, Yutong
Yuan, Feng
Gong, Ruolan
Wu, Jing
Zhang, Hua
Kang, Bin
Yuan, Guangyin
Zeng, Hui
Chen, Tongxin
author_facet Jin, Liang
Chen, Chenxin
Li, Yutong
Yuan, Feng
Gong, Ruolan
Wu, Jing
Zhang, Hua
Kang, Bin
Yuan, Guangyin
Zeng, Hui
Chen, Tongxin
author_sort Jin, Liang
collection PubMed
description Mg-based alloys might be ideal biomaterials in clinical applications owing to favorable mechanical properties, biodegradability, biocompatibility, and especially their anti-inflammatory properties. However, the precise signaling mechanism underlying the inhibition of inflammation by Mg-based alloys has not been elucidated. Here, we investigated the effects of a Mg-2.1Nd-0.2Zn-0.5Zr alloy (denoted as JDBM) on lipopolysaccharide (LPS)-induced macrophages. THP-1 cell-derived macrophages were cultured on JDBM, Ti−6Al−4V alloy (Ti), 15% extract of JDBM, and 7.5 mM of MgCl(2) for 1 h before the addition of LPS for an indicated time; the experiments included negative and positive controls. Our results showed JDBM, extract, and MgCl(2) could decrease LPS-induced tumor necrosis factor (TNF) and interleukin (IL)-6 expression. However, there were no morphologic changes in macrophages on Ti or JDBM. Mechanically, extract and MgCl(2) downregulated the expression of toll-like receptor (TLR)-4 and MYD88 compared with the positive control and inhibited LPS-induced nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways by inactivation of the phosphorylation of IKK-α/β, IKβ-α, P65, P38, and JNK. Additionally, the LPS-induced reactive oxygen species (ROS) expression was also decreased by extract and MgCl(2). Interestingly, the expression of LPS-induced TNF and IL-6 could be recovered by knocking down TRPM7 of macrophages, in the presence of extract or MgCl(2). Mechanically, the activities of AKT and AKT1 were increased by extract or MgCl(2) with LPS and were blocked by a PI3K inhibitor, whereas siRNA TRPM7 inhibited only AKT1. Together, our results demonstrated the degradation products of Mg-based alloy, especially magnesium, and resolved inflammation by activation of the TRPM7–PI3K–AKT1 signaling pathway, which may be a potential advantage or target to promote biodegradable Mg-based alloy applications.
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spelling pubmed-69020942019-12-17 A Biodegradable Mg-Based Alloy Inhibited the Inflammatory Response of THP-1 Cell-Derived Macrophages Through the TRPM7–PI3K–AKT1 Signaling Axis Jin, Liang Chen, Chenxin Li, Yutong Yuan, Feng Gong, Ruolan Wu, Jing Zhang, Hua Kang, Bin Yuan, Guangyin Zeng, Hui Chen, Tongxin Front Immunol Immunology Mg-based alloys might be ideal biomaterials in clinical applications owing to favorable mechanical properties, biodegradability, biocompatibility, and especially their anti-inflammatory properties. However, the precise signaling mechanism underlying the inhibition of inflammation by Mg-based alloys has not been elucidated. Here, we investigated the effects of a Mg-2.1Nd-0.2Zn-0.5Zr alloy (denoted as JDBM) on lipopolysaccharide (LPS)-induced macrophages. THP-1 cell-derived macrophages were cultured on JDBM, Ti−6Al−4V alloy (Ti), 15% extract of JDBM, and 7.5 mM of MgCl(2) for 1 h before the addition of LPS for an indicated time; the experiments included negative and positive controls. Our results showed JDBM, extract, and MgCl(2) could decrease LPS-induced tumor necrosis factor (TNF) and interleukin (IL)-6 expression. However, there were no morphologic changes in macrophages on Ti or JDBM. Mechanically, extract and MgCl(2) downregulated the expression of toll-like receptor (TLR)-4 and MYD88 compared with the positive control and inhibited LPS-induced nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways by inactivation of the phosphorylation of IKK-α/β, IKβ-α, P65, P38, and JNK. Additionally, the LPS-induced reactive oxygen species (ROS) expression was also decreased by extract and MgCl(2). Interestingly, the expression of LPS-induced TNF and IL-6 could be recovered by knocking down TRPM7 of macrophages, in the presence of extract or MgCl(2). Mechanically, the activities of AKT and AKT1 were increased by extract or MgCl(2) with LPS and were blocked by a PI3K inhibitor, whereas siRNA TRPM7 inhibited only AKT1. Together, our results demonstrated the degradation products of Mg-based alloy, especially magnesium, and resolved inflammation by activation of the TRPM7–PI3K–AKT1 signaling pathway, which may be a potential advantage or target to promote biodegradable Mg-based alloy applications. Frontiers Media S.A. 2019-12-03 /pmc/articles/PMC6902094/ /pubmed/31849975 http://dx.doi.org/10.3389/fimmu.2019.02798 Text en Copyright © 2019 Jin, Chen, Li, Yuan, Gong, Wu, Zhang, Kang, Yuan, Zeng and Chen. 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
Jin, Liang
Chen, Chenxin
Li, Yutong
Yuan, Feng
Gong, Ruolan
Wu, Jing
Zhang, Hua
Kang, Bin
Yuan, Guangyin
Zeng, Hui
Chen, Tongxin
A Biodegradable Mg-Based Alloy Inhibited the Inflammatory Response of THP-1 Cell-Derived Macrophages Through the TRPM7–PI3K–AKT1 Signaling Axis
title A Biodegradable Mg-Based Alloy Inhibited the Inflammatory Response of THP-1 Cell-Derived Macrophages Through the TRPM7–PI3K–AKT1 Signaling Axis
title_full A Biodegradable Mg-Based Alloy Inhibited the Inflammatory Response of THP-1 Cell-Derived Macrophages Through the TRPM7–PI3K–AKT1 Signaling Axis
title_fullStr A Biodegradable Mg-Based Alloy Inhibited the Inflammatory Response of THP-1 Cell-Derived Macrophages Through the TRPM7–PI3K–AKT1 Signaling Axis
title_full_unstemmed A Biodegradable Mg-Based Alloy Inhibited the Inflammatory Response of THP-1 Cell-Derived Macrophages Through the TRPM7–PI3K–AKT1 Signaling Axis
title_short A Biodegradable Mg-Based Alloy Inhibited the Inflammatory Response of THP-1 Cell-Derived Macrophages Through the TRPM7–PI3K–AKT1 Signaling Axis
title_sort biodegradable mg-based alloy inhibited the inflammatory response of thp-1 cell-derived macrophages through the trpm7–pi3k–akt1 signaling axis
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6902094/
https://www.ncbi.nlm.nih.gov/pubmed/31849975
http://dx.doi.org/10.3389/fimmu.2019.02798
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