PDK1/mTOR Signaling in Myeloid Cells Differentially Regulates the Early and Late Stages of Sepsis
The cecal ligation and perforation (CLP) model is the gold standard for the polymicrobial sepsis. In the CLP mice, the myeloid cells play an important role in septic shock. The phenotypes and the activation state of the macrophage and neutrophil correlate with their metabolism. In the present study,...
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| Format: | Article |
| Language: | English |
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Wiley
2020-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2020/5437175 |
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| author | Juan Du Guoli Li Mingxi Hua Junyan Han Yu Hao Hui Zeng Ang Li Yaxian Kong |
| author_facet | Juan Du Guoli Li Mingxi Hua Junyan Han Yu Hao Hui Zeng Ang Li Yaxian Kong |
| author_sort | Juan Du |
| collection | DOAJ |
| description | The cecal ligation and perforation (CLP) model is the gold standard for the polymicrobial sepsis. In the CLP mice, the myeloid cells play an important role in septic shock. The phenotypes and the activation state of the macrophage and neutrophil correlate with their metabolism. In the present study, we generated the specific myeloid deletion of PDK1 and mTOR mice, which was the important regulator of metabolic signaling. We found that the deletion of PDK1 in the myeloid cells could aggravate the early septic shock in the CLP mice, as well as the deletion of mTORC1 and mTORC2. Moreover, PDK1 deletion attenuated the inflammation induced by LPS in the late stage on CLP mice, which was exacerbated in mTORC1 and mTORC2 knockout mice. Both PDK1 and mTORC1/2 could not only regulate the cellular metabolism but also play important roles on the myeloid cells in the secondary stimulation of sepsis. The present study will provide a theoretical prospect for the therapy of the septic shock in different stages. |
| format | Article |
| id | doaj-art-1de17b2feffc4e2e88abb13cdc705166 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2020-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-1de17b2feffc4e2e88abb13cdc7051662025-02-03T01:05:08ZengWileyMediators of Inflammation0962-93511466-18612020-01-01202010.1155/2020/54371755437175PDK1/mTOR Signaling in Myeloid Cells Differentially Regulates the Early and Late Stages of SepsisJuan Du0Guoli Li1Mingxi Hua2Junyan Han3Yu Hao4Hui Zeng5Ang Li6Yaxian Kong7Beijing Key Laboratory of Emerging Infectious Diseases, Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, ChinaBeijing Key Laboratory of Emerging Infectious Diseases, Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, ChinaBeijing Key Laboratory of Emerging Infectious Diseases, Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, ChinaBeijing Key Laboratory of Emerging Infectious Diseases, Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, ChinaBeijing Key Laboratory of Emerging Infectious Diseases, Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, ChinaBeijing Key Laboratory of Emerging Infectious Diseases, Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, ChinaBeijing Key Laboratory of Emerging Infectious Diseases, Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, ChinaBeijing Key Laboratory of Emerging Infectious Diseases, Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, ChinaThe cecal ligation and perforation (CLP) model is the gold standard for the polymicrobial sepsis. In the CLP mice, the myeloid cells play an important role in septic shock. The phenotypes and the activation state of the macrophage and neutrophil correlate with their metabolism. In the present study, we generated the specific myeloid deletion of PDK1 and mTOR mice, which was the important regulator of metabolic signaling. We found that the deletion of PDK1 in the myeloid cells could aggravate the early septic shock in the CLP mice, as well as the deletion of mTORC1 and mTORC2. Moreover, PDK1 deletion attenuated the inflammation induced by LPS in the late stage on CLP mice, which was exacerbated in mTORC1 and mTORC2 knockout mice. Both PDK1 and mTORC1/2 could not only regulate the cellular metabolism but also play important roles on the myeloid cells in the secondary stimulation of sepsis. The present study will provide a theoretical prospect for the therapy of the septic shock in different stages.http://dx.doi.org/10.1155/2020/5437175 |
| spellingShingle | Juan Du Guoli Li Mingxi Hua Junyan Han Yu Hao Hui Zeng Ang Li Yaxian Kong PDK1/mTOR Signaling in Myeloid Cells Differentially Regulates the Early and Late Stages of Sepsis Mediators of Inflammation |
| title | PDK1/mTOR Signaling in Myeloid Cells Differentially Regulates the Early and Late Stages of Sepsis |
| title_full | PDK1/mTOR Signaling in Myeloid Cells Differentially Regulates the Early and Late Stages of Sepsis |
| title_fullStr | PDK1/mTOR Signaling in Myeloid Cells Differentially Regulates the Early and Late Stages of Sepsis |
| title_full_unstemmed | PDK1/mTOR Signaling in Myeloid Cells Differentially Regulates the Early and Late Stages of Sepsis |
| title_short | PDK1/mTOR Signaling in Myeloid Cells Differentially Regulates the Early and Late Stages of Sepsis |
| title_sort | pdk1 mtor signaling in myeloid cells differentially regulates the early and late stages of sepsis |
| url | http://dx.doi.org/10.1155/2020/5437175 |
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