Indoleamine 2, 3-dioxygenase 1 activation in macrophage exacerbates hepatic ischemia-reperfusion injury by triggering hepatocyte ferroptosis
Copyright © 2024 Elsevier B.V. All rights reserved..
BACKGROUND: Hepatic Ischemia-reperfusion (I/R) injury, critical challenge in liver surgery and transplantation, exerts a significant impact on the prognosis and survival of patients. Inflammation and cell death play pivotal roles in pathogenesis of hepatic I/R injury. Indoleamine 2, 3-dioxygenase 1 (IDO-1), a key enzyme involved in the kynurenine pathway, has been extensively investigated for its regulatory effects on innate immune responses and cell ferroptosis. However, the precise involvement of IDO-1 in hepatic I/R injury remains unclear.
METHODS: IDO-1 knockout mice were generated to establish a murine model of liver partial warm ischemia and reperfusion, while an in vitro Hypoxia/Reoxygenation (H/R) model was employed to simulate ischemia/reperfusion injury.
RESULTS: The involvement of ferroptosis was observed to be involved in hepatic I/R injury, and effective mitigation of liver injury was achieved through the inhibition of ferroptosis. In the context of hepatic I/R injury, up-regulation of IDO-1 was found in macrophages exhibiting prominent M1 polarization and impaired efferocytosis. Deficiency or inhibition of IDO-1 alleviated hepatocytes ferroptosis and M1 polarization induced by hepatic I/R injury, while also enhancing M2 polarization and promoting efferocytosis in macrophages. Furthermore, depletion of macrophages attenuated ferroptosis in hepatocytes induced by hepatic I/R injury.
CONCLUSION: This study highlights the crucial role of IDO-1 activation in macrophages in triggering ferroptosis in hepatocytes during hepatic ischemia-reperfusion injury. Our findings suggest that targeting IDO-1 could be a promising therapeutic strategy for mitigating hepatic I/R injury associated with liver surgery and transplantation.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:130 |
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| Enthalten in: |
International immunopharmacology - 130(2024) vom: 30. März, Seite 111692 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Ma, Shuoyi [VerfasserIn] |
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| Links: |
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| Themen: |
3-dioxygenase 1 |
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| Anmerkungen: |
Date Completed 25.03.2024 Date Revised 27.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.intimp.2024.111692 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a Copyright © 2024 Elsevier B.V. All rights reserved. | ||
| 520 | |a BACKGROUND: Hepatic Ischemia-reperfusion (I/R) injury, critical challenge in liver surgery and transplantation, exerts a significant impact on the prognosis and survival of patients. Inflammation and cell death play pivotal roles in pathogenesis of hepatic I/R injury. Indoleamine 2, 3-dioxygenase 1 (IDO-1), a key enzyme involved in the kynurenine pathway, has been extensively investigated for its regulatory effects on innate immune responses and cell ferroptosis. However, the precise involvement of IDO-1 in hepatic I/R injury remains unclear | ||
| 520 | |a METHODS: IDO-1 knockout mice were generated to establish a murine model of liver partial warm ischemia and reperfusion, while an in vitro Hypoxia/Reoxygenation (H/R) model was employed to simulate ischemia/reperfusion injury | ||
| 520 | |a RESULTS: The involvement of ferroptosis was observed to be involved in hepatic I/R injury, and effective mitigation of liver injury was achieved through the inhibition of ferroptosis. In the context of hepatic I/R injury, up-regulation of IDO-1 was found in macrophages exhibiting prominent M1 polarization and impaired efferocytosis. Deficiency or inhibition of IDO-1 alleviated hepatocytes ferroptosis and M1 polarization induced by hepatic I/R injury, while also enhancing M2 polarization and promoting efferocytosis in macrophages. Furthermore, depletion of macrophages attenuated ferroptosis in hepatocytes induced by hepatic I/R injury | ||
| 520 | |a CONCLUSION: This study highlights the crucial role of IDO-1 activation in macrophages in triggering ferroptosis in hepatocytes during hepatic ischemia-reperfusion injury. Our findings suggest that targeting IDO-1 could be a promising therapeutic strategy for mitigating hepatic I/R injury associated with liver surgery and transplantation | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a 3-dioxygenase 1 | |
| 650 | 4 | |a Ferroptosis | |
| 650 | 4 | |a Hepatic Ischemia-reperfusion injury | |
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| 700 | 1 | |a Ye, Haixin |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Chaofeng |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Jia |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Shu |e verfasserin |4 aut | |
| 700 | 1 | |a Song, Yuhong |e verfasserin |4 aut | |
| 700 | 1 | |a Gu, Yong |e verfasserin |4 aut | |
| 700 | 1 | |a Gao, Lei |e verfasserin |4 aut | |
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