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Rapamycin Exacerbates Staphylococcus aureus Pneumonia by Inhibiting mTOR-RPS6 in Macrophages
PURPOSE: This study aimed to explore the effect of Rapamycin (Rapa) in Staphylococcus aureus (S. aureus) pneumonia and clarify its possible mechanism. METHODS: We investigated the effects of Rapa on S. aureus pneumonia in mouse models and in macrophages cultured in vitro. Two possible mechanisms wer...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10695130/ http://dx.doi.org/10.2147/JIR.S434483 |
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author | Yu, Fang-Yi Zheng, Kua Wu, Yin-Fang Gao, Shen-Wei Weng, Qing-Yu Zhu, Chen Wu, Yan-Ping Li, Miao Qin, Zhong-Nan Lou, Jia-Fei Chen, Zhi-Hua Ying, Song-Min Shen, Hua-Hao Li, Wen |
author_facet | Yu, Fang-Yi Zheng, Kua Wu, Yin-Fang Gao, Shen-Wei Weng, Qing-Yu Zhu, Chen Wu, Yan-Ping Li, Miao Qin, Zhong-Nan Lou, Jia-Fei Chen, Zhi-Hua Ying, Song-Min Shen, Hua-Hao Li, Wen |
author_sort | Yu, Fang-Yi |
collection | PubMed |
description | PURPOSE: This study aimed to explore the effect of Rapamycin (Rapa) in Staphylococcus aureus (S. aureus) pneumonia and clarify its possible mechanism. METHODS: We investigated the effects of Rapa on S. aureus pneumonia in mouse models and in macrophages cultured in vitro. Two possible mechanisms were investigated: the mTOR-RPS6 pathway phosphorylation and phagocytosis. Furthermore, for the mechanism verification in vivo, mice with specific Mtor knockout in myeloid cells were constructed for pneumonia models. RESULTS: Rapa exacerbated S. aureus pneumonia in mouse models, promoting chemokines secretion and inflammatory cells infiltration in lung. In vitro, Rapa upregulated the secretion of chemokines and cytokines in macrophages induced by S. aureus. Mechanistically, the mTOR-ribosomal protein S6 (RPS6) pathway in macrophages was phosphorylated in response to S. aureus infection, and the inhibition of RPS6 phosphorylation upregulated the inflammation level. However, Rapa did not increase the phagocytic activity. Accordingly, mice with specific Mtor knockout in myeloid cells experienced more severe S. aureus pneumonia. CONCLUSION: Rapa exacerbates S. aureus pneumonia by increasing the inflammatory levels of macrophages. Inhibition of mTOR-RPS6 pathway upregulates the expression of cytokines and chemokines in macrophages, thus increases inflammatory cells infiltration and exacerbates tissue damage. |
format | Online Article Text |
id | pubmed-10695130 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Dove |
record_format | MEDLINE/PubMed |
spelling | pubmed-106951302023-12-05 Rapamycin Exacerbates Staphylococcus aureus Pneumonia by Inhibiting mTOR-RPS6 in Macrophages Yu, Fang-Yi Zheng, Kua Wu, Yin-Fang Gao, Shen-Wei Weng, Qing-Yu Zhu, Chen Wu, Yan-Ping Li, Miao Qin, Zhong-Nan Lou, Jia-Fei Chen, Zhi-Hua Ying, Song-Min Shen, Hua-Hao Li, Wen J Inflamm Res Original Research PURPOSE: This study aimed to explore the effect of Rapamycin (Rapa) in Staphylococcus aureus (S. aureus) pneumonia and clarify its possible mechanism. METHODS: We investigated the effects of Rapa on S. aureus pneumonia in mouse models and in macrophages cultured in vitro. Two possible mechanisms were investigated: the mTOR-RPS6 pathway phosphorylation and phagocytosis. Furthermore, for the mechanism verification in vivo, mice with specific Mtor knockout in myeloid cells were constructed for pneumonia models. RESULTS: Rapa exacerbated S. aureus pneumonia in mouse models, promoting chemokines secretion and inflammatory cells infiltration in lung. In vitro, Rapa upregulated the secretion of chemokines and cytokines in macrophages induced by S. aureus. Mechanistically, the mTOR-ribosomal protein S6 (RPS6) pathway in macrophages was phosphorylated in response to S. aureus infection, and the inhibition of RPS6 phosphorylation upregulated the inflammation level. However, Rapa did not increase the phagocytic activity. Accordingly, mice with specific Mtor knockout in myeloid cells experienced more severe S. aureus pneumonia. CONCLUSION: Rapa exacerbates S. aureus pneumonia by increasing the inflammatory levels of macrophages. Inhibition of mTOR-RPS6 pathway upregulates the expression of cytokines and chemokines in macrophages, thus increases inflammatory cells infiltration and exacerbates tissue damage. Dove 2023-11-30 /pmc/articles/PMC10695130/ http://dx.doi.org/10.2147/JIR.S434483 Text en © 2023 Yu 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 Yu, Fang-Yi Zheng, Kua Wu, Yin-Fang Gao, Shen-Wei Weng, Qing-Yu Zhu, Chen Wu, Yan-Ping Li, Miao Qin, Zhong-Nan Lou, Jia-Fei Chen, Zhi-Hua Ying, Song-Min Shen, Hua-Hao Li, Wen Rapamycin Exacerbates Staphylococcus aureus Pneumonia by Inhibiting mTOR-RPS6 in Macrophages |
title | Rapamycin Exacerbates Staphylococcus aureus Pneumonia by Inhibiting mTOR-RPS6 in Macrophages |
title_full | Rapamycin Exacerbates Staphylococcus aureus Pneumonia by Inhibiting mTOR-RPS6 in Macrophages |
title_fullStr | Rapamycin Exacerbates Staphylococcus aureus Pneumonia by Inhibiting mTOR-RPS6 in Macrophages |
title_full_unstemmed | Rapamycin Exacerbates Staphylococcus aureus Pneumonia by Inhibiting mTOR-RPS6 in Macrophages |
title_short | Rapamycin Exacerbates Staphylococcus aureus Pneumonia by Inhibiting mTOR-RPS6 in Macrophages |
title_sort | rapamycin exacerbates staphylococcus aureus pneumonia by inhibiting mtor-rps6 in macrophages |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10695130/ http://dx.doi.org/10.2147/JIR.S434483 |
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