Role of NLRP3 inflammasome in inflammatory bowel diseases

Abstract

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.

NLRP3 Inflammasome and Inflammatory Diseases

“…A role for NLRP3 in diseases of the central nervous system is emerging, including Alzheimer's disease and Parkinson's disease [31,32]. Abnormal activation of the NLRP3 inflammasome might contribute to intestinal cancer, inflammatory diseases, and autoinflammatory diseases such as keratitis/conjunctivitis [16,[33][34][35][36]. In this review, NLRP3 regulation and activation, its proinflammatory role in inflammatory diseases, interactions with autophagy, and targeted therapeutic approaches in inflammatory diseases will be summarized.…”

Interplay between Cellular and Molecular Mechanisms Underlying Inflammatory Bowel Diseases Development—A Focus on Ulcerative Colitis

“…As PRRs recognize DAMPs and PAMPs and CAS-1 is activated, NLRP3 inflammasome starts assembly, which leads to excessively production of IL-1β and IL-18 cytokines by epithelial cells—Paneth cells or antigen-presenting cells. A high number of these cytokines is associated with inflammation, by engaging and activating immune cells, as well as promoting pro-inflammatory cytokines and chemokines production [ 14 , 19 ]. Consequently, an increased level of IL-1β and IL-18, as well as CAS-1, has been identified in the inflamed mucosa, respectively in the MPs and intestinal tissue of UC patients.…”

“…Moreover, patients with Nod2 mutations have been associated with defective Atg16L1 recruitment, leading to autophagy induction [ 31 ]. Therefore, NLRP3 inflammasome activation and single nucleotide polymorphism mutations in the Nlrp3 have been widely reported to be correlated with pathogenesis and progression of IBD, including UC [ 14 , 19 ].…”

A Novel Combination Therapy Using Rosuvastatin and Lactobacillus Combats Dextran Sodium Sulfate-Induced Colitis in High-Fat Diet-Fed Rats by Targeting the TXNIP/NLRP3 Interaction and Influencing Gut Microbiome Composition

“…One theory explaining the pathogenesis of IBDs, especially UC, is an imbalance that exists in the gut microbiota, which leads to a persistent inflammatory response [ 4 ]. As a component of innate immunity, the inflammasome is a multiprotein oligomer responsible for activating inflammatory reactions, such as those present in UC [ 5 ]. Among the various inflammasome subtypes, the nucleotide-binding oligomerization domain (NOD)-, leucine-rich repeat (LRR)- and pyrin domain-containing protein 3 (NLRP3) represents a sensitive sensor of microbial and other danger signals and plays a crucial role in the mucosal immune response to promote the maturation of the pro-inflammatory cytokines, interleukin-1β (IL-1β) and IL-18 [ 6 ].…”