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zVAD alleviates experimental autoimmune hepatitis in mice by increasing the sensitivity of macrophage to TNFR1-dependent necroptosis by Xuehui Li; Yongting Zhang; Jinping Wang; Yuyu Li; Yuchong Wang; Fan Shi; Liang Hong; Lanjuan Li; Hongyan Diao is a Medicine article available to read on EtoBox.
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## Background & aims: Autoimmune hepatitis (aih) is characterized by hepatocyte destruction, leading to lymphocyte and macrophage accumulation in the liver. macrophages are key drivers of aih. a membrane-permeable pan-caspase inhibitor, z-val-ala-dl-asp-fluoromethylketone (zvad), induces macrophage necroptosis in response to certain stimuli. however, the function of zvad in the pathogenesis of autoimmune hepatitis remains elusive. in this study, we aimed to evaluate the effect and explore the underlying mechanisms of zvad against aih. ## Methods: Murine acute autoimmune liver injury was established by concanavalin a (cona) injection. bone marrow-derived macrophages (bmdms) were used in adoptive cell transfer experiments. the mechanism of action of zvad was examined using macrophage cell lines and bmdms. phosphorylation of mixed lineage kinase domain-like proteins was used as a marker of necroptosis. ## Results: Treatment with zvad increased necroptosis, reduced inflammatory cytokine production, and alleviated liver injury in a cona-induced liver injury mouse model. regardless of zvad treatment, macrophage deletion resulted in reduced neutrophil accumulation and relieved cona-induce
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- Author
- Xuehui Li; Yongting Zhang; Jinping Wang; Yuyu Li; Yuchong Wang; Fan Shi; Liang Hong; Lanjuan Li; Hongyan Diao
- Publisher
- Elsevier BV
- Published
- 2022
- Language
- EN
- Field
- Medicine (Health Sciences)