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Ac-SDKP Attenuates Activation of Lung Macrophages and Bone Osteoclasts in Rats Exposed to Silica by Inhibition of TLR4 and RANKL Signaling Pathways

BACKGROUND: Silica-induced inflammatory activation is associated with silicosis and various non-respiratory conditions. The present study was designed to examine the anti-inflammatory effects of N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) on lung macrophages and bone osteoclasts after silica inh...

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Autores principales: Jin, Fuyu, Geng, Fei, Xu, Dingjie, Li, Yaqian, Li, Tian, Yang, Xinyu, Liu, Shupeng, Zhang, Hui, Wei, Zhongqiu, Li, Shifeng, Gao, Xuemin, Cai, Wenchen, Mao, Na, Yi, Xue, Liu, Heliang, Sun, Ying, Yang, Fang, Xu, Hong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8088302/
https://www.ncbi.nlm.nih.gov/pubmed/33948088
http://dx.doi.org/10.2147/JIR.S306883
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author Jin, Fuyu
Geng, Fei
Xu, Dingjie
Li, Yaqian
Li, Tian
Yang, Xinyu
Liu, Shupeng
Zhang, Hui
Wei, Zhongqiu
Li, Shifeng
Gao, Xuemin
Cai, Wenchen
Mao, Na
Yi, Xue
Liu, Heliang
Sun, Ying
Yang, Fang
Xu, Hong
author_facet Jin, Fuyu
Geng, Fei
Xu, Dingjie
Li, Yaqian
Li, Tian
Yang, Xinyu
Liu, Shupeng
Zhang, Hui
Wei, Zhongqiu
Li, Shifeng
Gao, Xuemin
Cai, Wenchen
Mao, Na
Yi, Xue
Liu, Heliang
Sun, Ying
Yang, Fang
Xu, Hong
author_sort Jin, Fuyu
collection PubMed
description BACKGROUND: Silica-induced inflammatory activation is associated with silicosis and various non-respiratory conditions. The present study was designed to examine the anti-inflammatory effects of N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) on lung macrophages and bone osteoclasts after silica inhalation in rats. METHODS: Wistar rats and NR8383 and RAW 264.7 cell lines were used in the present study. The receptor activator of nuclear factor kappa-B ligand (RANKL) and toll-like receptor 4 (TLR4) signaling pathways was measured in the lung tissue of rats or NR8383/RAW 264.7 cells exposed to silica. The microarchitecture of the trabecular bone in the tibia and femur was evaluated in silicotic rats. Furthermore, the roles of Ac-SDKP on silicotic rats, silica-treated NR8383/RAW 264.7 cells, and RANKL-induced osteoclast differentiation were studied. RESULTS: The data indicated that silica inhalation might activate the RANKL and TLR4 signaling pathways in lung macrophages, thus inducing the lung inflammatory and proteolytic phenotype of macrophages and osteoclasts in lung and bone. Ac-SDKP maintained the lung elastin level by inhibiting lung inflammation and macrophage activation via the RANKL and TLR4 signaling pathways. Ac-SDKP also attenuated the reduction in femoral bone mineral density in silicotic rats by inhibiting osteoclast differentiation via the RANKL signaling pathway. CONCLUSION: Our findings support the hypothesis that inhalation of crystalline silica induces activation of lung macrophages and bone osteoclasts via the RANKL and TLR4 signaling pathways. Ac-SDKP has the potential to stabilize lung homeostasis and bone metabolism.
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spelling pubmed-80883022021-05-03 Ac-SDKP Attenuates Activation of Lung Macrophages and Bone Osteoclasts in Rats Exposed to Silica by Inhibition of TLR4 and RANKL Signaling Pathways Jin, Fuyu Geng, Fei Xu, Dingjie Li, Yaqian Li, Tian Yang, Xinyu Liu, Shupeng Zhang, Hui Wei, Zhongqiu Li, Shifeng Gao, Xuemin Cai, Wenchen Mao, Na Yi, Xue Liu, Heliang Sun, Ying Yang, Fang Xu, Hong J Inflamm Res Original Research BACKGROUND: Silica-induced inflammatory activation is associated with silicosis and various non-respiratory conditions. The present study was designed to examine the anti-inflammatory effects of N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) on lung macrophages and bone osteoclasts after silica inhalation in rats. METHODS: Wistar rats and NR8383 and RAW 264.7 cell lines were used in the present study. The receptor activator of nuclear factor kappa-B ligand (RANKL) and toll-like receptor 4 (TLR4) signaling pathways was measured in the lung tissue of rats or NR8383/RAW 264.7 cells exposed to silica. The microarchitecture of the trabecular bone in the tibia and femur was evaluated in silicotic rats. Furthermore, the roles of Ac-SDKP on silicotic rats, silica-treated NR8383/RAW 264.7 cells, and RANKL-induced osteoclast differentiation were studied. RESULTS: The data indicated that silica inhalation might activate the RANKL and TLR4 signaling pathways in lung macrophages, thus inducing the lung inflammatory and proteolytic phenotype of macrophages and osteoclasts in lung and bone. Ac-SDKP maintained the lung elastin level by inhibiting lung inflammation and macrophage activation via the RANKL and TLR4 signaling pathways. Ac-SDKP also attenuated the reduction in femoral bone mineral density in silicotic rats by inhibiting osteoclast differentiation via the RANKL signaling pathway. CONCLUSION: Our findings support the hypothesis that inhalation of crystalline silica induces activation of lung macrophages and bone osteoclasts via the RANKL and TLR4 signaling pathways. Ac-SDKP has the potential to stabilize lung homeostasis and bone metabolism. Dove 2021-04-27 /pmc/articles/PMC8088302/ /pubmed/33948088 http://dx.doi.org/10.2147/JIR.S306883 Text en © 2021 Jin et al. https://creativecommons.org/licenses/by-nc/3.0/This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/ (https://creativecommons.org/licenses/by-nc/3.0/) ). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
spellingShingle Original Research
Jin, Fuyu
Geng, Fei
Xu, Dingjie
Li, Yaqian
Li, Tian
Yang, Xinyu
Liu, Shupeng
Zhang, Hui
Wei, Zhongqiu
Li, Shifeng
Gao, Xuemin
Cai, Wenchen
Mao, Na
Yi, Xue
Liu, Heliang
Sun, Ying
Yang, Fang
Xu, Hong
Ac-SDKP Attenuates Activation of Lung Macrophages and Bone Osteoclasts in Rats Exposed to Silica by Inhibition of TLR4 and RANKL Signaling Pathways
title Ac-SDKP Attenuates Activation of Lung Macrophages and Bone Osteoclasts in Rats Exposed to Silica by Inhibition of TLR4 and RANKL Signaling Pathways
title_full Ac-SDKP Attenuates Activation of Lung Macrophages and Bone Osteoclasts in Rats Exposed to Silica by Inhibition of TLR4 and RANKL Signaling Pathways
title_fullStr Ac-SDKP Attenuates Activation of Lung Macrophages and Bone Osteoclasts in Rats Exposed to Silica by Inhibition of TLR4 and RANKL Signaling Pathways
title_full_unstemmed Ac-SDKP Attenuates Activation of Lung Macrophages and Bone Osteoclasts in Rats Exposed to Silica by Inhibition of TLR4 and RANKL Signaling Pathways
title_short Ac-SDKP Attenuates Activation of Lung Macrophages and Bone Osteoclasts in Rats Exposed to Silica by Inhibition of TLR4 and RANKL Signaling Pathways
title_sort ac-sdkp attenuates activation of lung macrophages and bone osteoclasts in rats exposed to silica by inhibition of tlr4 and rankl signaling pathways
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8088302/
https://www.ncbi.nlm.nih.gov/pubmed/33948088
http://dx.doi.org/10.2147/JIR.S306883
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