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NLRP3-Dependent and -Independent Processing of Interleukin (IL)-1β in Active Ulcerative Colitis

Citation

Ranson, N and Veldhuis, M and Mitchell, B and Fanning, S and Cook, AL and Kunde, D and Eri, R, NLRP3-Dependent and -Independent Processing of Interleukin (IL)-1β in Active Ulcerative Colitis, International Journal of Molecular Sciences, 20, (1) ISSN 1422-0067 (2019) [Refereed Article]

DOI: doi:10.3390/ijms20010057

Abstract

A contributing factor in the development of ulcerative colitis (UC) and Crohn’s disease (CD) is the disruption of innate and adaptive signaling pathways due to aberrant cytokine production. The cytokine, interleukin (IL)-1β, is highly inflammatory and its production is tightly regulated through transcriptional control and both inflammasome-dependent and inflammasome- independent proteolytic cleavage. In this study, qRT-PCR, immunohistochemistry, immunofluorescence confocal microscopy were used to (1) assess the mRNA expression of NLRP3, IL-1β, CASP1 and ASC in paired biopsies from UC and CD patient, and (2) the colonic localization and spatial relationship of NLRP3 and IL-1β in active and quiescent disease. NLRP3 and IL-1β were found to be upregulated in active UC and CD. During active disease, IL-1β was localized to the infiltrate of lamina propria immune cells, which contrasts with the near-exclusive epithelial cell layer expression during non-inflammatory conditions. In active disease, NLRP3 was consistently expressed within the neutrophils and other immune cells of the lamina propria and absent from the epithelial cell layer. The disparity in spatial localization of IL-1β and NLRP3, observed only in active UC, which is characterized by a neutrophil-dominated lamina propria cell population, implies inflammasome-independent processing of IL-1β. Consistent with other acute inflammatory conditions, these results suggest that blocking both caspase-1 and neutrophil-derived serine proteases may provide an additional therapeutic option for treating active UC.

Item Details

Item Type:Refereed Article
Keywords:IBD, Inflammasomes, NLRP3
Research Division:Biological Sciences
Research Group:Genetics
Research Field:Genetic Immunology
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Digestive System Disorders
UTAS Author:Ranson, N (Dr Nicole Ranson)
UTAS Author:Cook, AL (Associate Professor Tony Cook)
UTAS Author:Kunde, D (Dr Dale Kunde)
UTAS Author:Eri, R (Associate Professor Raj Eri)
ID Code:130885
Year Published:2019
Web of Science® Times Cited:2
Deposited By:Health Sciences
Deposited On:2019-02-19
Last Modified:2019-08-05
Downloads:0

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