---
_id: '3161'
abstract:
- lang: eng
  text: 'Some inflammatory stimuli trigger activation of the NLRP3 inflammasome by
    inducing efflux of cellular potassium. Loss of cellular potassium is known to
    potently suppress protein synthesis, leading us to test whether the inhibition
    of protein synthesis itself serves as an activating signal for the NLRP3 inflammasome.
    Murine bone marrow-derived macrophages, either primed by LPS or unprimed, were
    exposed to a panel of inhibitors of ribosomal function: ricin, cycloheximide,
    puromycin, pactamycin, and anisomycin. Macrophages were also exposed to nigericin,
    ATP, monosodium urate (MSU), and poly I:C. Synthesis of pro-IL-ß and release of
    IL-1ß from cells in response to these agents was detected by immunoblotting and
    ELISA. Release of intracellular potassium was measured by mass spectrometry. Inhibition
    of translation by each of the tested translation inhibitors led to processing
    of IL-1ß, which was released from cells. Processing and release of IL-1ß was reduced
    or absent from cells deficient in NLRP3, ASC, or caspase-1, demonstrating the
    role of the NLRP3 inflammasome. Despite the inability of these inhibitors to trigger
    efflux of intracellular potassium, the addition of high extracellular potassium
    suppressed activation of the NLRP3 inflammasome. MSU and double-stranded RNA,
    which are known to activate the NLRP3 inflammasome, also substantially inhibited
    protein translation, supporting a close association between inhibition of translation
    and inflammasome activation. These data demonstrate that translational inhibition
    itself constitutes a heretofore-unrecognized mechanism underlying IL-1ß dependent
    inflammatory signaling and that other physical, chemical, or pathogen-associated
    agents that impair translation may lead to IL-1ß-dependent inflammation through
    activation of the NLRP3 inflammasome. For agents that inhibit translation through
    decreased cellular potassium, the application of high extracellular potassium
    restores protein translation and suppresses activation of the NLRP inflammasome.
    For agents that inhibit translation through mechanisms that do not involve loss
    of potassium, high extracellular potassium suppresses IL-1ß processing through
    a mechanism that remains undefined.'
acknowledgement: "Supported by National Institutes of Health grants GM071338 (ML)
  and AI059355 (BM).\r\nWe acknowledge the expertise of Dr. Martina Ralle in Department
  of Biochemistry and Molecular Biology at OHSU for measurements of potassium using
  inductively coupled plasma mass spectrometry."
article_number: e36044
article_processing_charge: No
author:
- first_name: Meghan
  full_name: Vyleta, Meghan
  id: 418901AA-F248-11E8-B48F-1D18A9856A87
  last_name: Vyleta
- first_name: John
  full_name: Wong, John
  last_name: Wong
- first_name: Bruce
  full_name: Magun, Bruce
  last_name: Magun
citation:
  ama: Vyleta M, Wong J, Magun B. Suppression of ribosomal function triggers innate
    immune signaling through activation of the NLRP3 inflammasome. <i>PLoS One</i>.
    2012;7(5). doi:<a href="https://doi.org/10.1371/journal.pone.0036044">10.1371/journal.pone.0036044</a>
  apa: Vyleta, M., Wong, J., &#38; Magun, B. (2012). Suppression of ribosomal function
    triggers innate immune signaling through activation of the NLRP3 inflammasome.
    <i>PLoS One</i>. Public Library of Science. <a href="https://doi.org/10.1371/journal.pone.0036044">https://doi.org/10.1371/journal.pone.0036044</a>
  chicago: Vyleta, Meghan, John Wong, and Bruce Magun. “Suppression of Ribosomal Function
    Triggers Innate Immune Signaling through Activation of the NLRP3 Inflammasome.”
    <i>PLoS One</i>. Public Library of Science, 2012. <a href="https://doi.org/10.1371/journal.pone.0036044">https://doi.org/10.1371/journal.pone.0036044</a>.
  ieee: M. Vyleta, J. Wong, and B. Magun, “Suppression of ribosomal function triggers
    innate immune signaling through activation of the NLRP3 inflammasome,” <i>PLoS
    One</i>, vol. 7, no. 5. Public Library of Science, 2012.
  ista: Vyleta M, Wong J, Magun B. 2012. Suppression of ribosomal function triggers
    innate immune signaling through activation of the NLRP3 inflammasome. PLoS One.
    7(5), e36044.
  mla: Vyleta, Meghan, et al. “Suppression of Ribosomal Function Triggers Innate Immune
    Signaling through Activation of the NLRP3 Inflammasome.” <i>PLoS One</i>, vol.
    7, no. 5, e36044, Public Library of Science, 2012, doi:<a href="https://doi.org/10.1371/journal.pone.0036044">10.1371/journal.pone.0036044</a>.
  short: M. Vyleta, J. Wong, B. Magun, PLoS One 7 (2012).
date_created: 2018-12-11T12:01:45Z
date_published: 2012-05-14T00:00:00Z
date_updated: 2025-09-30T07:52:40Z
day: '14'
ddc:
- '610'
department:
- _id: SyCr
doi: 10.1371/journal.pone.0036044
external_id:
  isi:
  - '000305339400011'
file:
- access_level: open_access
  checksum: 30cef37e27eaa467f6571b3640282010
  content_type: application/pdf
  creator: system
  date_created: 2018-12-12T10:14:30Z
  date_updated: 2020-07-14T12:46:01Z
  file_id: '5082'
  file_name: IST-2012-97-v1+1_journal.pone.0036044.pdf
  file_size: 2984012
  relation: main_file
file_date_updated: 2020-07-14T12:46:01Z
fulldoi: https://doi.org/10.1371/journal.pone.0036044
has_accepted_license: '1'
intvolume: '         7'
isi: 1
issue: '5'
language:
- iso: eng
license: https://creativecommons.org/licenses/by/4.0/
month: '05'
oa: 1
oa_version: Published Version
publication: PLoS One
publication_status: published
publisher: Public Library of Science
publist_id: '3526'
pubrep_id: '97'
quality_controlled: '1'
scopus_import: '1'
status: public
title: Suppression of ribosomal function triggers innate immune signaling through
  activation of the NLRP3 inflammasome
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 7
year: '2012'
...