Next Article in Journal
Impact of pH Modification on Protein Polymerization and Structure–Function Relationships in Potato Protein and Wheat Gluten Composites
Previous Article in Journal
Innovative Strategy for 3D Transfection of Primary Human Stem Cells with BMP-2 Expressing Plasmid DNA: A Clinically Translatable Strategy for Ex Vivo Gene Therapy
Open AccessArticle

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

1
School of Health Sciences, University of Tasmania, Launceston, Tasmania 7250, Australia
2
Launceston General Hospital, Launceston, Tasmania 7250, Australia
3
Wicking Dementia Research and Education Centre, Faculty of Health, University of Tasmania, Hobart, Tasmania 7000, Australia
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(1), 57; https://doi.org/10.3390/ijms20010057
Received: 13 November 2018 / Revised: 11 December 2018 / Accepted: 18 December 2018 / Published: 23 December 2018
(This article belongs to the Section Molecular Immunology)
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. View Full-Text
Keywords: NLRP3 inflammasome; Interleukin (IL)-1β; ulcerative colitis (UC); Crohn’s disease (CD); innate immune system NLRP3 inflammasome; Interleukin (IL)-1β; ulcerative colitis (UC); Crohn’s disease (CD); innate immune system
Show Figures

Figure 1

MDPI and ACS Style

Ranson, N.; Veldhuis, M.; Mitchell, B.; Fanning, S.; Cook, A.L.; Kunde, D.; Eri, R. NLRP3-Dependent and -Independent Processing of Interleukin (IL)-1β in Active Ulcerative Colitis. Int. J. Mol. Sci. 2019, 20, 57.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop