Ethyl pyruvate ameliorates acute respiratory distress syndrome in mice
Copyright © 2024 Elsevier B.V. All rights reserved..
Acute respiratory distress syndrome (ARDS) became a focus of intensive research due to its death toll during the Covid-19 pandemic. An uncontrolled and excessive inflammatory response mediated by proinflammatory molecules such as high mobility group box protein 1 (HMGB1), IL-6, and TNF mounts as a response to infection. In this study, ethyl pyruvate (EP), a known inhibitor of HMGB1, was tested in the model of murine ARDS induced in C57BL/6 mice by intranasal administration of polyinosinic:polycytidylic acid (poly(I:C)). Intraperitoneal administration of EP ameliorated the ARDS-related histopathological changes in the lungs of poly(I:C)-induced ARDS and decreased numbers of immune cells in the lungs, broncho-alveolar lavage fluid and draining lymph nodes (DLN). Specifically, fewer CD8+ T cells and less activated CD4+ T cells were observed in DLN. Consequently, the lungs of EP-treated animals had fewer damage-inflicting CD8+ cells and macrophages. Additionally, the expression and production of proinflammatory cytokines, IL-17, IFN-γ and IL-6 were downregulated in the lungs. The expression of chemokine CCL5 which recruits immune cells into the lungs was also reduced. Finally, EP downregulated the expression of HMGB1 in the lungs. Our results imply that EP should be further evaluated as a potential candidate for ARDS therapy.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:971 |
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| Enthalten in: |
European journal of pharmacology - 971(2024) vom: 15. Apr., Seite 176509 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Mićanović, Dragica [VerfasserIn] |
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| Links: |
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| Themen: |
03O98E01OB |
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| Anmerkungen: |
Date Completed 22.04.2024 Date Revised 22.04.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.ejphar.2024.176509 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM369836057 |
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| 520 | |a Acute respiratory distress syndrome (ARDS) became a focus of intensive research due to its death toll during the Covid-19 pandemic. An uncontrolled and excessive inflammatory response mediated by proinflammatory molecules such as high mobility group box protein 1 (HMGB1), IL-6, and TNF mounts as a response to infection. In this study, ethyl pyruvate (EP), a known inhibitor of HMGB1, was tested in the model of murine ARDS induced in C57BL/6 mice by intranasal administration of polyinosinic:polycytidylic acid (poly(I:C)). Intraperitoneal administration of EP ameliorated the ARDS-related histopathological changes in the lungs of poly(I:C)-induced ARDS and decreased numbers of immune cells in the lungs, broncho-alveolar lavage fluid and draining lymph nodes (DLN). Specifically, fewer CD8+ T cells and less activated CD4+ T cells were observed in DLN. Consequently, the lungs of EP-treated animals had fewer damage-inflicting CD8+ cells and macrophages. Additionally, the expression and production of proinflammatory cytokines, IL-17, IFN-γ and IL-6 were downregulated in the lungs. The expression of chemokine CCL5 which recruits immune cells into the lungs was also reduced. Finally, EP downregulated the expression of HMGB1 in the lungs. Our results imply that EP should be further evaluated as a potential candidate for ARDS therapy | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a BALF | |
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| 700 | 1 | |a Kulaš, Jelena |e verfasserin |4 aut | |
| 700 | 1 | |a Despotović, Sanja |e verfasserin |4 aut | |
| 700 | 1 | |a Stegnjaić, Goran |e verfasserin |4 aut | |
| 700 | 1 | |a Jevtić, Bojan |e verfasserin |4 aut | |
| 700 | 1 | |a Koprivica, Ivan |e verfasserin |4 aut | |
| 700 | 1 | |a Mirkov, Ivana |e verfasserin |4 aut | |
| 700 | 1 | |a Stanisavljević, Suzana |e verfasserin |4 aut | |
| 700 | 1 | |a Nikolovski, Neda |e verfasserin |4 aut | |
| 700 | 1 | |a Miljković, Đorđe |e verfasserin |4 aut | |
| 700 | 1 | |a Saksida, Tamara |e verfasserin |4 aut | |
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