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NLRP3 inhibitors as potential therapeutic agents for treatment of inflammatory bowel disease


Perera, AP and Kunde, D and Eri, R, NLRP3 inhibitors as potential therapeutic agents for treatment of inflammatory bowel disease, Current Pharmaceutical Design, 23, (16) pp. 2321-2327. ISSN 1381-6128 (2017) [Refereed Article]

Copyright Statement

© 2017 Bentham Science Publishers

DOI: doi:10.2174/1381612823666170201162414


Background: Inflammatory bowel disease (IBD) is a group of intestinal disorders characterised by chronic relapsing inflammation of the small intestine and colon. IBD manifests as either ulcerative colitis or Crohn’s disease and increases the risk of developing colorectal cancer.

Methods: Here, we have reviewed current treatment regimen for IBD utilising anti-inflammatory drugs, immune system suppressors and antibiotics or a combination of these. However, these therapeutics lead to a number of adverse effects, remission or significant non-responsiveness creating an urgent need to develop potent drugs with novel mechanisms of action for IBD.

Results: The inflammasome is a multiprotein complex that assembles to a key innate immune system signalling platform and is involved in the pathogenesis of inflammatory and autoimmune diseases. A number of investigations show that the NLRP3 inflammasome recognizes microbial and cell stress components and serve as a platform for caspase-1 activation and pro-inflammatory cytokine IL-1β, IL18 maturation. Although the exact aetiology of IBD is unknown, uncontrolled NLRP3 Inflammasome activation has shown to play a major role in the chronic intestinal inflammation and mature IL-1β and IL18 are consistently associated with increased colitis and colitis associated colorectal cancer development.

Conclusion: In this review, we discuss the experimental NLRP3 inhibitors that have been investigated in IBD experimental models. The potential mechanism of action of these inhibitors such as inhibiting NF-κB activation and decreasing mitochondrial reactive oxygen species are discussed in detail. We further expand the controversial role of NLRP3 in IBD and future issues that might arise from the long term use of NLRP3 inhibitors in IBD therapy.

Item Details

Item Type:Refereed Article
Keywords:inflammatory bowel disease, NLRP3 inflammasome, NLRP3 inhibitors, chronic colitis, colorectal cancer, interleukin-1 beta, interleukin-18
Research Division:Biomedical and Clinical Sciences
Research Group:Immunology
Research Field:Innate immunity
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Perera, AP (Mrs Agampodi Perera)
UTAS Author:Kunde, D (Dr Dale Kunde)
UTAS Author:Eri, R (Associate Professor Raj Eri)
ID Code:127174
Year Published:2017
Web of Science® Times Cited:28
Deposited By:Health Sciences
Deposited On:2018-07-16
Last Modified:2020-01-03

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