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Inhibiting caspase-3/GSDME-mediated pyroptosis ameliorates septic lung injury in mice model.
- Source :
-
Molecular immunology [Mol Immunol] 2024 Aug; Vol. 172, pp. 96-104. Date of Electronic Publication: 2024 Jul 02. - Publication Year :
- 2024
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Abstract
- Acute lung injury is one of the most serious complications of sepsis, which is a common critical illness in clinic. This study aims to investigate the role of caspase-3/ gasdermin-E (GSDME)-mediated pyroptosis in sepsis-induced lung injury in mice model. Cecal ligation (CLP) operation was used to establish mice sepsis-induced lung injury model. Lung coefficient, hematoxylin and eosin staining and transmission electron microscopy were used to observe the lung injury degree. In addition, caspase-3-specific inhibitor Z-DEVD-FMK and GSDME-derived inhibitor AC-DMLD-CMK were used in CLP model, caspase-3 activity, GSDME immunofluorescence, serum lactate dehydrogenase (LDH) and interleukin-6 (IL-6) levels, TUNEL staining, and the expression levels of GSDME related proteins were detected. The mice in CLP group showed the increased expressions of cleaved-caspase-3 and GSDME-N terminal, destruction of lung structure, and the increases of LDH, IL-6, IL-18 and IL-1β levels, which were improved in mice treated with Z-DEVD-FMK or AC-DMLD-CMK. In conclusion, caspase-3/GSDME mediated pyroptosis is involved in the occurrence of sepsis-induced lung injury in mice model, inhibiting caspase-3 or GSDME can both alleviate lung injury.<br />Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interest regarding the publication of this paper.<br /> (Copyright © 2024 Elsevier Ltd. All rights reserved.)
Details
- Language :
- English
- ISSN :
- 1872-9142
- Volume :
- 172
- Database :
- MEDLINE
- Journal :
- Molecular immunology
- Publication Type :
- Academic Journal
- Accession number :
- 38954890
- Full Text :
- https://doi.org/10.1016/j.molimm.2024.06.007