Nrf2 Deficiency Exacerbated CLP-Induced Pulmonary Injury and Inflammation through Autophagy- and NF-κB/PPARγ-Mediated Macrophage Polarization
The balance between M1 and M2 macrophage polarization is involved in the regulation of pulmonary inflammation. Nuclear factor erythroid-derived 2-like 2 (Nfe2l2, also known as Nrf2), a nuclear transcription factor, is reported to play protective roles in acute lung injury (ALI) and inflammation, and...
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MDPI AG
2022-12-01
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| Online Access: | https://www.mdpi.com/2073-4409/11/23/3927 |
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| author | Jing Luo Jin Wang Jing Zhang Aming Sang Xujun Ye Zhenshun Cheng Xinyi Li |
| author_facet | Jing Luo Jin Wang Jing Zhang Aming Sang Xujun Ye Zhenshun Cheng Xinyi Li |
| author_sort | Jing Luo |
| collection | DOAJ |
| description | The balance between M1 and M2 macrophage polarization is involved in the regulation of pulmonary inflammation. Nuclear factor erythroid-derived 2-like 2 (Nfe2l2, also known as Nrf2), a nuclear transcription factor, is reported to play protective roles in acute lung injury (ALI) and inflammation, and increasing evidence indicates that the protective effects of Nrf2 are closely related to autophagy. This study aimed to explore whether Nrf2 is involved in sepsis-induced acute pulmonary injury and inflammation and in the role of macrophage polarization in the process. In the present study, sepsis patients, an Nrf2 knockout mouse that underwent cecal ligation and puncture (CLP), and lipopolysaccharide (LPS)-treated macrophage cell lines were employed to investigate the potential functions of Nrf2 in sepsis-induced lung injury and the underlying mechanisms. Clinical studies showed that the NRF2 mRNA level was inversely correlated with pulmonary inflammation and disease severity in patients with sepsis. Analyses in a CLP-treated Nrf2 knockout mouse model indicated that an Nrf2 deficiency promoted a CLP-induced increase in M1 macrophage polarization and apoptosis and inhibited CLP-induced upregulation of the autophagy level in lung tissues. Experiments in RAW264.7 cells revealed that Nrf2 overexpression inhibited M1 macrophage polarization but promoted M2 macrophage polarization by improving the autophagy, and Nrf2 overexpression promoted PPARγ but inhibited NF-κB nuclear translocation. In conclusion, these results indicate that Nrf2 plays a protective role in sepsis-induced pulmonary injury and inflammation through the regulation of autophagy- and NF-κB/PPARγ-mediated macrophage polarization. |
| first_indexed | 2024-03-09T17:50:41Z |
| format | Article |
| id | doaj.art-b3dd15a5c486416487f3c522848b1c27 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T17:50:41Z |
| publishDate | 2022-12-01 |
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| record_format | Article |
| series | Cells |
| spelling | doaj.art-b3dd15a5c486416487f3c522848b1c272023-11-24T10:46:08ZengMDPI AGCells2073-44092022-12-011123392710.3390/cells11233927Nrf2 Deficiency Exacerbated CLP-Induced Pulmonary Injury and Inflammation through Autophagy- and NF-κB/PPARγ-Mediated Macrophage PolarizationJing Luo0Jin Wang1Jing Zhang2Aming Sang3Xujun Ye4Zhenshun Cheng5Xinyi Li6Department of Anesthesiology, Zhongnan Hospital of Wuhan University, Wuhan 430071, ChinaDepartment of Anesthesiology, Zhongnan Hospital of Wuhan University, Wuhan 430071, ChinaDepartment of Anesthesiology, Zhongnan Hospital of Wuhan University, Wuhan 430071, ChinaDepartment of Anesthesiology, Zhongnan Hospital of Wuhan University, Wuhan 430071, ChinaDepartment of Geriatrics, Zhongnan Hospital of Wuhan University, Wuhan 430071, ChinaDepartment of Respiratory and Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan 430071, ChinaDepartment of Anesthesiology, Zhongnan Hospital of Wuhan University, Wuhan 430071, ChinaThe balance between M1 and M2 macrophage polarization is involved in the regulation of pulmonary inflammation. Nuclear factor erythroid-derived 2-like 2 (Nfe2l2, also known as Nrf2), a nuclear transcription factor, is reported to play protective roles in acute lung injury (ALI) and inflammation, and increasing evidence indicates that the protective effects of Nrf2 are closely related to autophagy. This study aimed to explore whether Nrf2 is involved in sepsis-induced acute pulmonary injury and inflammation and in the role of macrophage polarization in the process. In the present study, sepsis patients, an Nrf2 knockout mouse that underwent cecal ligation and puncture (CLP), and lipopolysaccharide (LPS)-treated macrophage cell lines were employed to investigate the potential functions of Nrf2 in sepsis-induced lung injury and the underlying mechanisms. Clinical studies showed that the NRF2 mRNA level was inversely correlated with pulmonary inflammation and disease severity in patients with sepsis. Analyses in a CLP-treated Nrf2 knockout mouse model indicated that an Nrf2 deficiency promoted a CLP-induced increase in M1 macrophage polarization and apoptosis and inhibited CLP-induced upregulation of the autophagy level in lung tissues. Experiments in RAW264.7 cells revealed that Nrf2 overexpression inhibited M1 macrophage polarization but promoted M2 macrophage polarization by improving the autophagy, and Nrf2 overexpression promoted PPARγ but inhibited NF-κB nuclear translocation. In conclusion, these results indicate that Nrf2 plays a protective role in sepsis-induced pulmonary injury and inflammation through the regulation of autophagy- and NF-κB/PPARγ-mediated macrophage polarization.https://www.mdpi.com/2073-4409/11/23/3927Nrf2acute lung injurypulmonary inflammationautophagymacrophage polarization |
| spellingShingle | Jing Luo Jin Wang Jing Zhang Aming Sang Xujun Ye Zhenshun Cheng Xinyi Li Nrf2 Deficiency Exacerbated CLP-Induced Pulmonary Injury and Inflammation through Autophagy- and NF-κB/PPARγ-Mediated Macrophage Polarization Cells Nrf2 acute lung injury pulmonary inflammation autophagy macrophage polarization |
| title | Nrf2 Deficiency Exacerbated CLP-Induced Pulmonary Injury and Inflammation through Autophagy- and NF-κB/PPARγ-Mediated Macrophage Polarization |
| title_full | Nrf2 Deficiency Exacerbated CLP-Induced Pulmonary Injury and Inflammation through Autophagy- and NF-κB/PPARγ-Mediated Macrophage Polarization |
| title_fullStr | Nrf2 Deficiency Exacerbated CLP-Induced Pulmonary Injury and Inflammation through Autophagy- and NF-κB/PPARγ-Mediated Macrophage Polarization |
| title_full_unstemmed | Nrf2 Deficiency Exacerbated CLP-Induced Pulmonary Injury and Inflammation through Autophagy- and NF-κB/PPARγ-Mediated Macrophage Polarization |
| title_short | Nrf2 Deficiency Exacerbated CLP-Induced Pulmonary Injury and Inflammation through Autophagy- and NF-κB/PPARγ-Mediated Macrophage Polarization |
| title_sort | nrf2 deficiency exacerbated clp induced pulmonary injury and inflammation through autophagy and nf κb pparγ mediated macrophage polarization |
| topic | Nrf2 acute lung injury pulmonary inflammation autophagy macrophage polarization |
| url | https://www.mdpi.com/2073-4409/11/23/3927 |
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