Fig. 4

Schematic representation of the relationship between inflammation and NASH disease progression. Upon stimulation with TNF-α, the NF-κB pathway is activated, as indicated by phosphorylation and nuclear translocation of NF-κB and transcription of its target genes, including IL-6 and IL-1β. Newly synthesized IL-6 is secreted by cells and binds to the IL-6R in an autocrine or paracrine manner, leading to activation of the IL-6R/gp130 complex and intracellular JAK1/2 kinases. STAT3 proteins are then phosphorylated by JAK1/2, dimerize, enter the nucleus, and initiate transcription of STAT3-dependent genes such as TGF-β, IL-6, IL-17, and IL-1β, which contribute to the development of inflammatory responses Alternatively, the first signal for NLRP3 inflammasome activation is NF-κB-mediated NLRP3 transcription. When activated, the NLRP3 inflammasome converts caspase-1, pro-IL-18, and pro-IL-1β into active forms, triggering an inflammatory response. IL-6R interleukin-6 receptor, gp130 glycoprotein 130