Inhibiting caspase-3/GSDME-mediated pyroptosis ameliorates septic lung injury in mice model

  • Mol Immunol. 2024 Aug:172:96-104. doi: 10.1016/j.molimm.2024.06.007.
Hongqian Qin  1 ,  Na Lu  1 ,  Kai Chen  1 ,  Yuhui Huang  2 ,  Yan Rui  3 ,  Linian Huang  1 ,  Qin Gao  4 ,  Junfeng Hu  5
Affiliations
  • 1. Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital of Bengbu Medical University, China; Anhui Province Key Laboratory of Clinical and Preclinical Research in Respiratory Disease, China; Clinical Research Center for Respiratory Disease (tumor) in Anhui Province, 287 Changhuai Road, Anhui 233004, China.
  • 2. Department of Physiology, Bengbu Medical University, China; Key Laboratory of Cardiovascular and cerebrovascular Diseases, Bengbu Medical University, 2600 Donghai Avenue, Anhui 233030, China.
  • 3. Clinical Research Center for Respiratory Disease (tumor) in Anhui Province, 287 Changhuai Road, Anhui 233004, China.
  • 4. Department of Physiology, Bengbu Medical University, China; Key Laboratory of Cardiovascular and cerebrovascular Diseases, Bengbu Medical University, 2600 Donghai Avenue, Anhui 233030, China. Electronic address: [email protected].
  • 5. Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital of Bengbu Medical University, China; Anhui Province Key Laboratory of Clinical and Preclinical Research in Respiratory Disease, China; Clinical Research Center for Respiratory Disease (tumor) in Anhui Province, 287 Changhuai Road, Anhui 233004, China. Electronic address: [email protected].
PMID: 38954890 DOI: 10.1016/j.molimm.2024.06.007
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.

Keywords
Caspase-3; GSDME; Pyroptosis; Sepsis induced lung injury.
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