Translational pediatrics · 2026
A preliminary study on NLRP3 activation and the interventional effects of MCC950 in Con A-induced EAH mice.
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Ma Di, Liu Xinglou, Ai Guo, Liu Lingling, Huang Yuan, Liao Yi, Lu Yuanyuan, Zhang Zhan, Zhou Hua, Shu Sainan, Fang Feng
Аннотация
BACKGROUND: MCC950 is a selective inhibitor of the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome; however, its effects have not been explored in concanavalin A (Con A)-induced experimental autoimmune hepatitis (EAH) in mice. This study aims to investigate the involvement of the NLRP3 inflammasome pathway in the pathogenesis of Con A-induced EAH and to assess the therapeutic potential and mechanistic actions of MCC950 in this model.
METHODS: An EAH mouse model was established via Con A injection to investigate its pathogenesis. Mice were divided into four groups: control, MCC950, Con A, and Con A + MCC950. Liver and blood samples were collected at 0, 6, 12, and 24 hours post-injection. Multiple techniques were employed, including hematoxylin and eosin (HE) staining, enzyme-linked immunosorbent assay (ELISA), western blot, quantitative real-time polymerase chain reaction (qPCR), immunohistochemistry (IHC), and a FAM-FLICA caspase-1 activity assay. These approaches were used to evaluate liver histopathology, serum transaminase levels, expression of NLRP3 inflammasome pathway components, and the extent of pyroptosis.
RESULTS: In the Con A-induced EAH mouse model, significant increases in serum transaminase levels, the extent of liver histopathological damage, the expression of NLRP3, caspase-1, interleukin (IL)-1β, and IL-18, as well as pyroptosis activity levels, were observed at 12 hours post-injection compared to baseline (0 hours) (P<0.05). Following MCC950 treatment, all these parameters were markedly reduced relative to the Con A-only group (P<0.05), indicating a protective effect of NLRP3 inhibition in this model.
CONCLUSIONS: MCC950 exerts a hepatoprotective effect in the Con A-induced EAH mouse model by suppressing the NLRP3 inflammasome pathway and reducing pyroptosis.
METHODS: An EAH mouse model was established via Con A injection to investigate its pathogenesis. Mice were divided into four groups: control, MCC950, Con A, and Con A + MCC950. Liver and blood samples were collected at 0, 6, 12, and 24 hours post-injection. Multiple techniques were employed, including hematoxylin and eosin (HE) staining, enzyme-linked immunosorbent assay (ELISA), western blot, quantitative real-time polymerase chain reaction (qPCR), immunohistochemistry (IHC), and a FAM-FLICA caspase-1 activity assay. These approaches were used to evaluate liver histopathology, serum transaminase levels, expression of NLRP3 inflammasome pathway components, and the extent of pyroptosis.
RESULTS: In the Con A-induced EAH mouse model, significant increases in serum transaminase levels, the extent of liver histopathological damage, the expression of NLRP3, caspase-1, interleukin (IL)-1β, and IL-18, as well as pyroptosis activity levels, were observed at 12 hours post-injection compared to baseline (0 hours) (P<0.05). Following MCC950 treatment, all these parameters were markedly reduced relative to the Con A-only group (P<0.05), indicating a protective effect of NLRP3 inhibition in this model.
CONCLUSIONS: MCC950 exerts a hepatoprotective effect in the Con A-induced EAH mouse model by suppressing the NLRP3 inflammasome pathway and reducing pyroptosis.