Emerging insights into molecular mechanisms underlying pyroptosis and functions of inflammasomes in diseases

• Published in: Journal of cellular physiology Vol. 235; no. 4; pp. 3207 - 3221
• Main Authors: Lu, Fangfang, Lan, Zhixin, Xin, Zhaoqi, He, Chunrong, Guo, Zimeng, Xia, Xiaobo, Hu, Tu
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.04.2020
• Subjects: Adaptor Proteins, Signal Transducing - genetics; Apoptosis; Apoptosis - genetics; Apoptosis Regulatory Proteins - genetics; Autoimmune diseases; Calcium-Binding Proteins - genetics; CARD Signaling Adaptor Proteins - genetics; Caspase; caspases; Caspases - genetics; Caspases - metabolism; Cell death; Cell size; Cytokines; Cytotoxicity; GSDMD; Humans; Infectious diseases; Inflammasomes; Inflammasomes - genetics; Inflammasomes - metabolism; Inflammation - genetics; Inflammation - metabolism; Inflammation - pathology; Interleukin-18 - genetics; Interleukin-1beta - genetics; Intracellular Signaling Peptides and Proteins - genetics; Membranes; Microorganisms; Molecular modelling; NLR Family, Pyrin Domain-Containing 3 Protein - genetics; Oligomerization; Phosphate-Binding Proteins - genetics; Plasma membranes; Pore formation; Pyrin protein; Pyroptosis; Pyroptosis - genetics; Sepsis; Substrates; GSDMD; pyroptosis; inflammasomes; caspases
• ISSN: 0021-9541; 1097-4652; 1097-4652
• DOI: 10.1002/jcp.29268

Pyroptosis is a form of necrotic and inflammatory programmed cell death, which could be characterized by cell swelling, pore formation on plasma membranes, and release of proinflammatory cytokines (IL‐1β and IL‐18). The process of pyroptosis presents as dual effects: protecting multicellular organisms from microbial infection and endogenous dangers; leading to pathological inflammation if overactivated. Two pathways have been found to trigger pyroptosis: caspase‐1 mediated inflammasome pathway with the involvement of NLRP1‐, NLRP3‐, NLRC4‐, AIM2‐, pyrin‐inflammasome (canonical inflammasome pathway) and caspase‐4/5/11‐mediated inflammasome pathway (noncanonical inflammasome pathway). Gasdermin D (GSDMD) has been proved to be a substrate of inflammatory caspases (caspase‐1/4/5/11), and the cleaved N‐terminal domain of GSDMD oligomerizes to form cytotoxic pores on the plasma membrane. Here, we mainly reviewed the up to date mechanisms of pyroptosis, and began with the inflammasomes as the activator of caspase‐1/caspase‐11, 4, and 5. We further discussed these inflammasomes functions in diseases, including infectious diseases, sepsis, inflammatory autoimmune diseases, and neuroinflammatory diseases. We summarized the updated molecular mechanisms implicated in the regulation of inflammasomes which present as the activators of canonical/noncanonical inflammasome pathways of pyroptosis, and these inflammasomes function in relevant infectious, autoinflammatory, and neuroinflammatory diseases.