Molecularly Distinct NLRP3 Inducers Mediate Diverse Ratios of Interleukin-1 β and Interleukin-18 from Human Monocytes

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Midtbö, Kristine,1991-Örebro universitet,Institutionen för medicinska vetenskaper,Inflammatory Response and Infection Susceptibility Centre (iRiSC) (author)

Molecularly Distinct NLRP3 Inducers Mediate Diverse Ratios of Interleukin-1 β and Interleukin-18 from Human Monocytes

Article/chapterEnglish2020

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Hindawi Publishing Corporation,2020
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LIBRIS-ID:oai:DiVA.org:oru-87225
https://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-87225URI
https://doi.org/10.1155/2020/4651090DOI

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Language:English
Summary in:English

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Subject category:ref swepub-contenttype
Subject category:art swepub-publicationtype

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Funding Agency:Örebro University ORU 2.2.1-4060/2013 ORU 2018/01219
Inflammasomes cleave and activate interleukin- (IL-) 1β and IL-18 which have both shared and unique biological functions. IL-1β 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-1β has served as the prototypic indicator of inflammasome activation, few studies have compared the potential differences in IL-1β 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-1β 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-1β, 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-1β ratio. The difference in the IL-18 : IL-1β 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-1β and IL-18 into account and moving away from an on/off perspective of inflammasome activation.

Subject headings and genre

NATURVETENSKAP Biologi Immunologi hsv//swe
NATURAL SCIENCES Biological Sciences Immunology hsv//eng

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Eklund, Daniel,1984-Örebro universitet,Institutionen för medicinska vetenskaper,Inflammatory Response and Infection Susceptibility Centre (iRiSC)(Swepub:oru)ded (author)
Särndahl, Eva,1963-Örebro universitet,Institutionen för medicinska vetenskaper(Swepub:oru)easl (author)
Persson, Alexander,1978-Örebro universitet,Institutionen för medicinska vetenskaper,Inflammatory Response and Infection Susceptibility Centre (iRiSC)(Swepub:oru)axpn (author)
Örebro universitetInstitutionen för medicinska vetenskaper (creator_code:org_t)

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In:Mediators of Inflammation: Hindawi Publishing Corporation20200962-93511466-1861

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