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NLRP3 inflammasome in colitis and colitis-associated colorectal cancer

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Abstract

A low level of inflammation is an integral part of the balance between the immune system and the microbiota in the high antigen environment of the gastrointestinal tract and maintains homeostasis. A failure of this balance can lead to chronic intestinal inflammation and increase the chances to develop colorectal cancer significantly. The underlying mechanisms that link inflammation and carcinogenesis are not clear but the molecular platforms of the inflammasomes have been implicated. Inflammasomes are molecule complexes that are assembled in response to microbial components or cellular danger signals and facilitate the production of bioactive pro-inflammatory cytokines. One inflammasome in particular, NLRP3, has been analysed extensively in its contribution to colitis and has been shown to be associated with the development of colitis-associated colorectal cancer. This review will summarise the role of NLRP3 in intestinal inflammation, discuss some of the triggers of inflammation in the gastrointestinal tract such as diet and introduce some opportunities to use this inflammasome as therapeutic target for the treatment of colitis and colitis-associated colorectal cancer.

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Funding

The funding was provided by John Stewart Bowel Cancer Research Grant.

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Author notes

  1. Agampodi Promoda Perera and Karishma Sajnani: equal first authors.

  2. Rajaraman Eri and Heinrich Korner: share senior authorship.

Authors and Affiliations

  1. School of Health Sciences, University of Tasmania, Launceston, TAS, Australia

    Agampodi Promoda Perera & Rajaraman Eri

  2. Menzies Institute for Medical Research, University of Tasmania, MS2, 17 Liverpool St, Hobart, TAS, 7000, Australia

    Karishma Sajnani, Joanne Dickinson & Heinrich Körner

  3. Key Laboratory of Anti-inflammatory and Immunopharmacology, Ministry of Education, Engineering Technology Research Centre of Anti-inflammatory and Immunodrugs in Anhui Province, Institute of Clinical Pharmacology, Anhui Medical University, Hefei, Anhui, People’s Republic of China

    Heinrich Körner

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  1. Agampodi Promoda Perera
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  2. Karishma Sajnani
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  3. Joanne Dickinson
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Perera, A.P., Sajnani, K., Dickinson, J. et al. NLRP3 inflammasome in colitis and colitis-associated colorectal cancer. Mamm Genome 29, 817–830 (2018). https://doi.org/10.1007/s00335-018-9783-2

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