The ‘speck’-tacular oversight of the NLRP3-pyroptosis pathway on gastrointestinal inflammatory diseases and tumorigenesis

Journal of Biomedical Science

Review

Valentina Arrè¹  Matteo Centonze¹  Roberto Negro¹  Rosanna Scialpi¹  Maria Principia Scavo¹  Gianluigi Giannelli² 

[1] Personalized Medicine Laboratory, National Institute of Gastroenterology “S. de Bellis”, IRCCS Research Hospital, Via Turi 27, 70013, Castellana Grotte, BA, Italy;Scientific Direction, National Institute of Gastroenterology “S. de Bellis”, IRCCS Research Hospital, Via Turi 27, 70013, Castellana Grotte, BA, Italy;

关键词: Inflammasome;    NLRP3;    Gasdermin D;    Pyroptosis;    Intestinal Bowel Disease;    Gastrointestinal cancer;   

DOI  :  10.1186/s12929-023-00983-7

 received in 2023-08-30, accepted in 2023-10-23,  发布年份 2023

来源: Springer

【 摘 要 】

The NLRP3 inflammasome is an intracellular sensor and an essential component of the innate immune system involved in danger recognition. An important hallmark of inflammasome activation is the formation of a single supramolecular punctum, known as a speck, per cell, which is the site where the pro-inflammatory cytokines IL-1β and IL-18 are converted into their bioactive form. Speck also provides the platform for gasdermin D protein activation, whose N-terminus domain perforates the plasma membrane, allowing the release of mature cytokines alongside with a highly inflammatory form of cell death, namely pyroptosis. Although controlled NLRP3 inflammasome-pyroptosis pathway activation preserves mucosal immunity homeostasis and contributes to host defense, a prolonged trigger is deleterious and could lead, in genetically predisposed subjects, to the onset of inflammatory bowel disease, including Crohn's disease and ulcerative colitis, as well as to gastrointestinal cancer. Experimental evidence shows that the NLRP3 inflammasome has both protective and pathogenic abilities. In this review we highlight the impact of the NLRP3-pyroptosis axis on the pathophysiology of the gastrointestinal tract at molecular level, focusing on newly discovered features bearing pro- and anti-inflammatory and neoplastic activity, and on targeted therapies tested in preclinical and clinical trials.

【 授权许可】

CC BY   
© The Author(s) 2023

【 图 表 】

Fig. 1

Fig. 1

12936_2016_1316_Article_IEq8.gif

Fig. 9

Fig. 2