The SMAC mimetic birinapant alleviates lipopolysaccharide-induced acute lung injury by inhibiting MAPK signaling
Copyright © 2023. Published by Elsevier B.V..
The second mitochondria-derived activator of caspases (SMAC) mimetic birinapant attenuated liver injury by inhibited the degradation of tumor necrosis factor receptor-associated factor 3 (TRAF3) and activation of mitogen-activated protein kinase (MAPK) signaling pathway in liver macrophage, but its role in LPS induced acute lung injury (ALI) is not understood. The present study was to investigate the effects of birinapant on ALI and its possible mechanism. A dose of birinapant (30 mg/kg) or a vehicle was administered intravenously 24 hours before LPS (100 μg) stimulation in mice. The levels of TNF-α, IL-6 and IL-1β in bronchoalveolar lavage fluid (BALF) were measured by ELISA. The infiltrated macrophages and expression of monocyte chemoattractant protein-1 (MCP-1) was determined by immunohistochemistry staining in the lung tissues. The JNK and p38 MAPK activation, protein expression and K48-linked polyubiquitination of TRAF3 were determined in alveolar macrophage cell line (MH-S cells) after 1μg/ml LPS stimulation. The results showed that the birinapant down-regulated the levels of TNF-α, IL-6 and IL-1β in the BALF. In addition, birinapant markedly inhibited macrophages infiltration and MCP-1 protein expression in lung tissues. At last, birinapant suppressed the MAPKsignaling pathway and K48-linked ubiquitinated degradation of TRAF3 in MH-S cells after LPS administration. In conclusion, the results proved that birinapant protected against LPS-induced ALI through inhibiting MAPK activation and K48-linked ubiquitination of TRAF3 in alveolar macrophages.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:264 |
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| Enthalten in: |
Immunology letters - 264(2023) vom: 15. Dez., Seite 31-35 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Hu, Hui [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 16.12.2023 Date Revised 16.12.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.imlet.2023.10.008 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a Copyright © 2023. Published by Elsevier B.V. | ||
| 520 | |a The second mitochondria-derived activator of caspases (SMAC) mimetic birinapant attenuated liver injury by inhibited the degradation of tumor necrosis factor receptor-associated factor 3 (TRAF3) and activation of mitogen-activated protein kinase (MAPK) signaling pathway in liver macrophage, but its role in LPS induced acute lung injury (ALI) is not understood. The present study was to investigate the effects of birinapant on ALI and its possible mechanism. A dose of birinapant (30 mg/kg) or a vehicle was administered intravenously 24 hours before LPS (100 μg) stimulation in mice. The levels of TNF-α, IL-6 and IL-1β in bronchoalveolar lavage fluid (BALF) were measured by ELISA. The infiltrated macrophages and expression of monocyte chemoattractant protein-1 (MCP-1) was determined by immunohistochemistry staining in the lung tissues. The JNK and p38 MAPK activation, protein expression and K48-linked polyubiquitination of TRAF3 were determined in alveolar macrophage cell line (MH-S cells) after 1μg/ml LPS stimulation. The results showed that the birinapant down-regulated the levels of TNF-α, IL-6 and IL-1β in the BALF. In addition, birinapant markedly inhibited macrophages infiltration and MCP-1 protein expression in lung tissues. At last, birinapant suppressed the MAPKsignaling pathway and K48-linked ubiquitinated degradation of TRAF3 in MH-S cells after LPS administration. In conclusion, the results proved that birinapant protected against LPS-induced ALI through inhibiting MAPK activation and K48-linked ubiquitination of TRAF3 in alveolar macrophages | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Acute lung injury | |
| 650 | 4 | |a Birinapant | |
| 650 | 4 | |a Lipopolysaccharide | |
| 650 | 4 | |a Macrophage | |
| 650 | 7 | |a Mitogen-Activated Protein Kinases |2 NLM | |
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| 650 | 7 | |a birinapant |2 NLM | |
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| 650 | 7 | |a Tumor Necrosis Factor-alpha |2 NLM | |
| 650 | 7 | |a Caspases |2 NLM | |
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| 650 | 7 | |a Interleukin-6 |2 NLM | |
| 650 | 7 | |a Interleukin-1beta |2 NLM | |
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| 700 | 1 | |a Li, Tao |e verfasserin |4 aut | |
| 700 | 1 | |a Shi, Li |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Peizhi |e verfasserin |4 aut | |
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