Figure 2.

Caspase-1-dependent and independent signaling pathways of pyroptosis. In the classical pathway, when the body is stimulated by hyperlipidemia, abnormal Ca²⁺ levels, and bacteria, infection cells activate downstream inflammatory bodies, including NLRP3 and AIM2 through PAMP and DAMP pathways. NLRP3 can establish a link with CARD and procaspase-1. Procaspase-1 bound to CARD can self-cleave into mature caspase-1, and AIM2 can directly activate caspase-1. Mature caspase-1 can cleave the downstream GSDMD and can induce large production of IL-18 and other inflammatory factors. The N-terminal of GSDMD, which is cleaved, will combine with phospholipids and protein on the cell membrane to form pores, leading to the outflow of inflammatory factors and cell contents. Inflammatory factors can activate T cell immunity in the body, further aggravate body damage, and eventually lead to cell death. The non-classical pathway of pyroptosis can be induced by LPS, which can activate caspase-4/5/11, and also lead to GSDMD cleavage. AIM2: Absent in melanoma 2; CARD: Caspase activation and recruitment domain; DAMP: Danger-associated molecular patterns; GSDMD: Gasdermin D; IL: Interleukin; LPS: Lipopolysaccharides; NLRP3: Nucleotide-binding oligomerization domain-like receptor protein 3; PAMP: Pathogen-associated molecular pattern.