Role of NLRP3 inflammasome in inflammatory bowel diseases

• Published in: World journal of gastroenterology : WJG Vol. 25; no. 33; pp. 4796 - 4804
• Main Authors: Tourkochristou, Evanthia, Aggeletopoulou, Ioanna, Konstantakis, Christos, Triantos, Christos
• Format: Journal Article
• Language: English
• Published: United States Baishideng Publishing Group Inc 07.09.2019
• Subjects: Adaptive Immunity; Animals; Anti-Inflammatory Agents - pharmacology; Anti-Inflammatory Agents - therapeutic use; Disease Models, Animal; Humans; Immunity, Innate; Immunity, Mucosal; Inflammasomes - drug effects; Inflammasomes - immunology; Inflammasomes - metabolism; Inflammatory Bowel Diseases - drug therapy; Inflammatory Bowel Diseases - genetics; Inflammatory Bowel Diseases - immunology; NLR Family, Pyrin Domain-Containing 3 Protein - genetics; NLR Family, Pyrin Domain-Containing 3 Protein - metabolism; Signal Transduction - drug effects; Signal Transduction - immunology; Interleukin 1β; Mucosal immune system; Inflammatory bowel diseases; NLRP3 gene polymorphisms; NLRP3 inflammasome; Interleukin 18
• ISSN: 1007-9327; 2219-2840; 2219-2840
• DOI: 10.3748/wjg.v25.i33.4796

Inflammasomes are multiprotein intracellular complexes which are responsible for the activation of inflammatory responses. Among various subtypes of inflammasomes, NLRP3 has been a subject of intensive investigation. NLRP3 is considered to be a sensor of microbial and other danger signals and plays a crucial role in mucosal immune responses, promoting the maturation of proinflammatory cytokines interleukin 1β (IL-1β) and IL-18. NLRP3 inflammasome has been associated with a variety of inflammatory and autoimmune conditions, including inflammatory bowel diseases (IBD). The role of NLRP3 in IBD is not yet fully elucidated as it seems to demonstrate both pathogenic and protective effects. Studies have shown a relationship between genetic variants and mutations in NLRP3 gene with IBD pathogenesis. A complex interaction between the NLRP3 inflammasome and the mucosal immune response has been reported. Activation of the inflammasome is a key function mediated by the innate immune response and in parallel the signaling through IL-1β and IL-18 is implicated in adaptive immunity. Further research is needed to delineate the precise mechanisms of NLRP3 function in regulating immune responses. Targeting NLRP3 inflammasome and its downstream signaling will provide new insights into the development of future therapeutic strategies.