Stellate Cells Orchestrate Concanavalin A-Induced Acute Liver Damage.

Stellate Cells Orchestrate Concanavalin A-Induced Acute Liver Damage. Am J Pathol. 2017 Jul 12;: Authors: Rani R, Tandon A, Wang J, Kumar S, Gandhi CR Abstract Concanavalin A (ConA) causes immune cell-mediated liver damage, but the contribution of resident nonparenchymal cells is also evident. Hepatic stellate cells (HSCs) induce hepatic inflammation and immunological reactions; we therefore investigated their role in ConA-induced liver injury. ConA was administered i.v. to control or HSC-depleted mice; hepatic histopathology and cytokines/chemokines were determined after 6 hours. In vitro, the effects of ConA-conditioned HSC medium on hepatocytes were determined. ConA induced robust inflammation, sinusoidal congestion, and extensive midzonal hepatocyte death in control mice, which were strongly minimized in HSC-depleted mice. CD4 and natural killer T cells and neutrophils were markedly reduced in ConA-treated HSC-depleted mice compared to control mice. The increase in cytokines and chemokines implicated in hepatic injury was much higher in ConA-treated control mice than in HSC-depleted mice. In vitro, ConA-treated HSCs showed increased expression of interferon-β, tumor necrosis factor-α, and CXCL1, induced oxidative stress in hepatocytes, and caused hepatocyte apoptosis. ConA induced nuclear translocation of interferon-regulatory factor-1 (IRF1) in hepatocytes in vivo, and ConA/HSC induced a similar effect in cultured hepato...
Source: The American Journal of Pathology - Category: Pathology Authors: Tags: Am J Pathol Source Type: research