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Induction of an Inflammatory Response in Primary Hepatocyte Cultures from Mice
Published on: March 10, 2017
CrmA gene expression protects mice against concanavalin-A-induced hepatitis by inhibiting IL-18 secretion and
M Fujino1, M Kawasaki, N Funeshima
1Department of Innovative Surgery, National Research Institute for Child Health and Development, Tokyo, Japan.
Abstract:
Activated cytotoxic T-cell-mediated hepatocyte apoptosis via Fas/Fas-ligand and perforin/granzyme pathways are believed to involve the model of concanavalin A (ConA)-induced hepatitis. The purpose of the present study is to investigate whether the cytokine response modifier A (crmA) gene effectively inhibits the hepatocyte apoptosis of ConA-induced hepatitis. We examined survival rates, liver pathology, immune histological changes, and cytokine profiles from mice receiving the recombinant adenovirus vectors containing cre and/or crmA genes, transferred to the liver 3 days before ConA injection, and a crmA gene nonexpression control group. Injection of ConA into mice rapidly led to massive hepatocyte apoptosis, and infiltration of leukocytes, especially CD11b(+) inflammatory cells. In contrast, liver damage was dramatically reduced in the mice that expressed the crmA gene. However, infiltration by CD4(+) cells was not affected. The survival of the mice increased significantly to 100% in the treated group versus the control group. Furthermore, we demonstrated that interleukin (IL)-18 plays an important role in ConA-induced hepatitis, and that crmA expression significantly inhibited IL-18 secretion. Our results showed that the crmA gene effectively inhibits apoptosis induced by ConA hepatitis. This indicates a potential therapeutic usage of crmA for protection from cellular damage due to hepatitis.
Insights
The cytokine response modifier A (crmA) gene significantly protects against concanavalin A (ConA)-induced hepatitis in mice. CrmA inhibits hepatocyte apoptosis and IL-18 secretion, improving survival rates.
Area of Science:
- Immunology
- Hepatology
- Molecular Biology
Background:
- Concanavalin A (ConA)-induced hepatitis is a model for cytotoxic T-cell-mediated hepatocyte apoptosis.
- Fas/Fas-ligand and perforin/granzyme pathways are implicated in this apoptotic process.
Purpose of the Study:
- To investigate the inhibitory effect of the cytokine response modifier A (crmA) gene on ConA-induced hepatitis.
- To assess the therapeutic potential of crmA in preventing liver damage.
Main Methods:
- Mice received recombinant adenovirus vectors expressing cre and/or crmA genes.
- ConA was injected 3 days post-gene transfer.
- Evaluated survival rates, liver pathology, immune histology, and cytokine profiles (including IL-18).
Main Results:
- ConA injection induced massive hepatocyte apoptosis and leukocyte infiltration.
- crmA gene expression significantly reduced liver damage and increased survival to 100%.
- crmA inhibited IL-18 secretion, while CD4(+) cell infiltration remained unaffected.
Conclusions:
- The crmA gene effectively inhibits apoptosis in ConA-induced hepatitis.
- crmA demonstrates potential as a therapeutic agent for protecting against hepatitis-induced cellular damage.
- Interleukin-18 plays a critical role in ConA-induced hepatitis pathogenesis.
