Concanavalin A hepatitis model

A tool for studying autoimmune hepatitis includes our Concanavalin (Con)-A model, which induces T cell mediated acute liver injury

A widely used experimental mouse model for acute immune-mediated hepatitis is achieved by intravenous injection of the plant lectin concanavalin A (ConA). In contrast to other models for acute hepatic damage, the ConA model has unique features in regards to its pathogenesis because it is primarily driven by the activation and recruitment of macrophages and T cells to the liver. Upon liver tissue infiltration, macrophages and T cells induced the secretion of several proinflammatory cytokines, such as TNFɑ, IFNγ, IL-1β and IL-2. Other prominent features of immune hepatitis include hepatocyte apoptosis, necrosis and leukocyte infiltration. 

In vivo Efficacy of Celastrol in a ConA Model

Experimental induction of a Concanavalin A hepatitis model. (A) Experimental strategy: preventative effects of the naturally occurring anti-inflammatory Celastrol were evaluated in a ConA induced liver injury model after 1 week of pre-treatment. (B) Celastrol treatment prevented increased alanine transaminase (ALT) and aspartate transaminase (AST) levels induced by ConA.

Analysis of Liver Immune Cells

Analysis of hepatic immune cells in a Concanavalin A hepatitis model. ConA administration alters the percentage of some immune cells. *P<0.05; **P<0.01; ***P<0.001 compared with the ConA group.

Effect of Celastrol on Cytokine Levels in a ConA Model

Assessment of inflammatory cytokines in a Concanavalin A hepatitis model. Celastrol treatment alleviates increased levels of some cytokines induced by ConA. *P<0.05; **P<0.01; ***P<0.001 compared with the ConA group.

Protective Effects of Celastrol in a ConA Model

Histologic evaluation of Celastrol in a ConA model. (A) Gross examination of the liver indicated abnormal pathology on ConA-treated me. (B) Histologic evaluation via H&E staining indicated significant presence of coagulative necrosis in the ConA model, while Celastrol-treated mice showed a less severe phenotype. (C) Quantitative scoring.

Celastrol Treatment Reduced Apoptosis in a ConA Model

Evaluation of TUNEL staining with Celastrol treatment in a ConA model. (A) Significantly reduced levels of TUNEL staining showed prevention of cell death in Celastrol-treated mice compared to the ConA model group. (B) Quantitative results. 

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