Molecularly Distinct NLRP3 Inducers Mediate Diverse Ratios of Interleukin-1β and Interleukin-18 from Human Monocytes. (22nd October 2020)

• Record Type: Journal Article
• Authors: Midtbö, Kristine; Eklund, Daniel; Särndahl, Eva; Persson, Alexander
• Other Names: Yi Young-Su Academic Editor.
• Is Part Of: Mediators of inflammation. Volume 2020(2020)
• Publication Date: 2020-10-22
• Subjects: Inflammation -- Mediators -- Periodicals; Biological response modifiers -- Periodicals; Inflammation (Pathologie) -- Médiateurs; Immunomodulateurs; Biological response modifiers; Inflammation -- Mediators; Immunology; Autacoids; Immunologic Factors; Cell Adhesion Molecules; Cell Communication; Cytokines; Inflammation; Periodicals; Electronic journals; 616.0473
• DOI: 10.1155/2020/4651090
• Languages: English
• ISSNs: 0962-9351

Abstract

Abstract : Inflammasomes cleave and activate interleukin- (IL-) 1 β and IL-18 which have both shared and unique biological functions. IL-1 β is an important mediator of the acute phase response to infections and tissue damage, whereas IL-18 takes part in activation and tailoring of the adaptive immune response. While IL-1 β has served as the prototypic indicator of inflammasome activation, few studies have compared the potential differences in IL-1 β and IL-18 production during inflammasome activation. Since these cytokines partake in different immune pathways, the involvement of inflammasome activity in different conditions needs to be described beyond IL-1 β production alone. To address a potential heterogeneity in inflammasome functionality, ATP, chitosan, or silica oxide (SiO2 ) were used to induce NLRP3 inflammasome activation in THP-1 cells and the subsequent outcomes were quantified. Despite using doses of the inflammasome inducers yielding similar release of IL-1 β, SiO2 -stimulated cells showed a lower concentration of released IL-18 compared to ATP and chitosan. Hence, the cells stimulated with SiO2 responded with a distinctly different IL-18 : IL-1 β ratio. The difference in the IL-18 : IL-1 β ratio for SiO2 was constant over different doses. While all downstream responses were strictly dependent on a functional NLRP3 inflammasome, the differences did not depend on the level of gene expression, caspase-1 activity, or pyroptosis. We suggest that the NLRP3 inflammasome response should be considered a dynamic process, which can be described by taking the ratio between IL-1 β and IL-18 into account and moving away from an on/off perspective of inflammasome activation.