Activation mechanism of the NLRP3 inflammasome

Activation mechanism of the NLRP3 inflammasome. Initiation signal (Signal 1): NLRP3 recognizes DAMPs and PAMPs, activating the NF-κB signaling pathway through mediating cytokines such as IL-1β and TNF-α. In turn, it promotes the activation of NLRP3, Pro-IL-18, and Pro-IL-1β, resulting in the expression of precursor proteins. Activation signal (Signal 2): The NLRP3 inflammasome is triggered through multiple pathways, including the ion activation pathway, mitochondrial damage with reactive oxygen species generation, and lysosome rupture. The NLRP3 inflammasome consists of three main components: the NLRP3 protein, ASC, and the effector molecule caspase-1. Upon activation, caspase-1 cleaves the precursors of IL-1β and IL-18, converting them into their active forms. Subsequently, IL-18 initiates subsequent signaling pathways, participating in various inflammatory reactions and exerting biological effects. Furthermore, NLRP3 can also stimulate caspase-1 to cleave GSDMD, forming N-GSDMD and triggering pyroptosis.

Publication

Autophagy and Inflammation: Regulatory Roles in Viral Infections (2023) Li Chen, et al. Biomolecules. 2023 Oct;13(10):1454. Figure: F3. Homo sapiens

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