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. Author manuscript; available in PMC: 2018 Jun 1.
Published in final edited form as: Immunol Res. 2017 Jun;65(3):739–749. doi: 10.1007/s12026-017-8913-3

Figure 8. Schematic illustration of signaling pathways by which Notch signaling may regulate NLRP3 inflammasome activation in APAP-induced liver injury.

Figure 8

Blocking Notch signaling by γ-secretase inhibitor DAPT suppresses the cleavage of Notch1 to NICD, which translocates into the nucleus to activate Notch target gene Hes1. Inhibition of Hes1 promotes HMGB1-TLR4 axis, which in turn triggers NLRP3 activation, leading to augmented caspase-1-mediated IL-1β secretion in APAP-induced liver inflammation. In addition, inhibition of Hes1 diminishes Stat3 and Akt phosphorylation, resulting in increased cell apoptosis/necrosis and reduced cell survival in APAP-challenged livers.