Biochemical and Biophysical Research Communications, Vol.521, No.2, 449-456, 2020
Critical role of IL-1 beta in the pathogenesis of Agrocybe aegerita galectin-induced liver injury through recruiting T cell to liver
Acute liver failure (ALF) can be the consequence of various etiologies, which immune response plays a pivotal role in the pathogenesis. For the diversity of etiologies, more animal models are still needed in this field. Here, we developed a new acute liver injury mouse model induced by a fungal lectin AAGL (Agrocybe aegerita galectin). Intravenous injection of AAGL could induce the infiltration and activation of T, NKT and NK cells in liver and T cell played an important role in the pathogenesis. However, compared with the widely used concanavalin A model, AAGL model showed different immune mechanism. Transcriptome analysis of live tissue suggested that inflammation mediated by chemokine and cytokine signaling pathway was different between AAGL and Con A model. Fluorescent quantitative PCR verification assay showed that IL-1 beta was expressed much higher in AAGL-treated mice and anti-IL-1 beta could ameliorate AAGL-induced liver injury by inhibiting NF-kappa B and p38 signaling pathway. The expression of CXCL9 which was responsible for T cell infiltration in liver was also inhibited in AAGL model. We found a critical role of IL-1 beta in the pathogenesis of AAGL model through recruiting T cells to liver, which highlighted that IL-1 beta antibody might be a candidate therapy for ALF. (C) 2019 Elsevier Inc. All rights reserved.