University Of Tasmania
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NLRP3-dependent and -independent processing of interleukin (IL)-1β in active ulcerative colitis

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journal contribution
posted on 2023-05-20, 00:58 authored by Nicole RansonNicole Ranson, Veldhuis, M, Mitchell, B, Fanning, S, Anthony CookAnthony Cook, Kunde, D, Rajaraman Eri
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.


Publication title

International Journal of Molecular Sciences








School of Health Sciences


Molecular Diversity Preservation International

Place of publication

Matthaeusstrasse 11, Basel, Switzerland, Ch-4057

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© 2018 by the authors. Licensee MDPI, Basel, Switzerland. Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0)

Repository Status

  • Open

Socio-economic Objectives

Clinical health not elsewhere classified; Clinical health not elsewhere classified

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