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Open AccessArticle

Parsing the IL-37-Mediated Suppression of Inflammasome Function

1
Department of Paediatrics, Monash University, Clayton, Victoria 3168, Australia
2
Ritchie Centre, Hudson Institute of Medical Research, Clayton, Victoria 3168, Australia
3
School of Pharmacy and Biomolecular Sciences, Royal College of Surgeons in Ireland, 123 St Stephens Green, Dublin 2, Ireland
4
Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Clayton, Victoria 3168, Australia
5
Department of Molecular and Translational Sciences, Monash University, Clayton, Victoria 3168, Australia
6
Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3168, Australia
7
Australian Research Council Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, Victoria 3168, Australia
8
Monash Newborn, Monash Children’s Hospital, Clayton, Victoria 3168, Australia
*
Author to whom correspondence should be addressed.
Cells 2020, 9(1), 178; https://doi.org/10.3390/cells9010178
Received: 30 November 2019 / Revised: 7 January 2020 / Accepted: 8 January 2020 / Published: 10 January 2020
(This article belongs to the Special Issue Mechanisms of Inflammasome Activation)
Interleukin (IL)-37 is a member of the IL-1 family of cytokines. Although its broad anti-inflammatory properties are well described, the effects of IL-37 on inflammasome function remain poorly understood. Performing gene expression analyses, ASC oligomerization/speck assays and caspase-1 assays in bone marrow-derived macrophages (BMDM), and employing an in vivo endotoxemia model, we studied how IL-37 affects the expression and maturation of IL-1β and IL-18, inflammasome activation, and pyroptosis in detail. IL-37 inhibited IL-1β production by NLRP3 and AIM2 inflammasomes, and IL-18 production by the NLRP3 inflammasome. This inhibition was partially attributable to effects on gene expression: whereas IL-37 did not affect lipopolysaccharide (LPS)-induced mRNA expression of Il18 or inflammasome components, IL-37-transgenic BMDM displayed an up to 83% inhibition of baseline and LPS-stimulated Il1b compared to their wild-type counterparts. Importantly, we observed that IL-37 suppresses nigericin- and silica-induced ASC oligomerization/speck formation (a step in inflammasome activation and subsequent caspase-1 activation), and pyroptosis (−50%). In mice subjected to endotoxemia, IL-37 inhibited plasma IL-1β (−78% compared to wild-type animals) and IL-18 (−61%). Thus, our study adds suppression of inflammasome activity to the portfolio of anti-inflammatory pathways employed by IL-37, highlighting this cytokine as a potential tool for treating inflammasome-driven diseases. View Full-Text
Keywords: interleukin 37; interleukin 1β; interleukin 18; inflammasome; ASC; caspase-1; pyroptosis; NLRP3; AIM2 interleukin 37; interleukin 1β; interleukin 18; inflammasome; ASC; caspase-1; pyroptosis; NLRP3; AIM2
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Rudloff, I.; Ung, H.K.; Dowling, J.K.; Mansell, A.; D’Andrea, L.; Ellisdon, A.M.; Whisstock, J.C.; Berger, P.J.; Nold-Petry, C.A.; Nold, M.F. Parsing the IL-37-Mediated Suppression of Inflammasome Function. Cells 2020, 9, 178.

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