Soluble egg antigen of Schistosoma japonicum induces pyroptosis in hepatic stellate cells by modulating ROS production

Autor: Renxian Tang, Delong Kong, Fanyun Kong, Jie Cui, Chao Yan, Xiang-Ye Liu, Kuiyang Zheng
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Liver Cirrhosis
0301 basic medicine
Programmed cell death
Snails
Liver fibrosis
Fluorescent Antibody Technique
Biology
Real-Time Polymerase Chain Reaction
Schistosoma japonicum
Flow cytometry
lcsh:Infectious and parasitic diseases
Mice
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Hepatic Stellate Cells
medicine
Pyroptosis
Animals
Schistosomiasis
lcsh:RC109-216
Propidium iodide
Liver injury
chemistry.chemical_classification
Analysis of Variance
Reactive oxygen species
medicine.diagnostic_test
Research
Caspase 1
ROS
medicine.disease
biology.organism_classification
Immunohistochemistry
Cell biology
Mice
Inbred C57BL
030104 developmental biology
Infectious Diseases
Liver
chemistry
Antigens
Helminth
Schistosomiasis japonica
030220 oncology & carcinogenesis
Hepatic stellate cell
Female
Parasitology
Reactive Oxygen Species
Zdroj: Parasites & Vectors, Vol 12, Iss 1, Pp 1-12 (2019)
Parasites & Vectors
ISSN: 1756-3305
Popis: Background Inflammation-induced dysfunction of hepatic stellate cells (HSCs) is involved in schistosomiasis-associated liver fibrosis, and soluble egg antigen (SEA) is a crucial pathogen-associated molecular pattern associated with liver injury in schistosomiasis. In addition, numerous studies have shown that caspase-1-mediated pyroptosis participates in the development of multiple inflammation-related diseases. However, whether pyroptotic cell death of HSCs is involved in SEA-mediated liver damage is not well understood. Methods Primary cultured HSCs and Schistosoma japonicum-infected mouse liver tissue were analysed for histological changes and caspase-1 activation, and the role of pyroptosis in the mechanisms underlying SEA-induced HSC death was investigated. Accumulation of reactive oxygen species (ROS) in infected livers and SEA-stimulated HSCs was measured by flow cytometry and immunofluorescence. Results Caspase-1 activity was elevated in both liver tissues and HSCs of S. japonicum-infected mice. Furthermore, SEA stimulation increased the proportion of pyroptotic HSCs, as shown by lactate dehydrogenase (LDH) release assays and by flow cytometric analysis of propidium iodide (PI) and caspase-1 double staining in cells. In addition, ROS generation was elevated in infected liver tissues and SEA-stimulated HSCs, and ROS inhibition downregulated SEA-induced caspase-1 activation and pyroptosis in HSCs. Conclusions Our present study demonstrates that pyroptotic cell death in HSCs induced by SEA via ROS-mediated caspase-1 activation may serve as a significant mechanism to initiate the inflammatory response and thereby exacerbate liver injury during S. japonicum infection.
Databáze: OpenAIRE
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