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Acidification changes affect the inflammasome in human nucleus pulposus cells

BACKGROUND: Interleukin (IL)-1β is involved in the pathology of intervertebral disc degeneration. Under normal conditions, IL-1β is present in cells in an inactive form (pro-IL-1β). However, under pathological conditions, pro-IL-1β is turned into its active form (IL-1β) by the inflammasome, a multi-...

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Autores principales: Brand, Frank J., Forouzandeh, Mahtab, Kaur, Harmanpreet, Travascio, Francesco, de Rivero Vaccari, Juan Pablo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4997758/
https://www.ncbi.nlm.nih.gov/pubmed/27563282
http://dx.doi.org/10.1186/s12950-016-0137-0
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author Brand, Frank J.
Forouzandeh, Mahtab
Kaur, Harmanpreet
Travascio, Francesco
de Rivero Vaccari, Juan Pablo
author_facet Brand, Frank J.
Forouzandeh, Mahtab
Kaur, Harmanpreet
Travascio, Francesco
de Rivero Vaccari, Juan Pablo
author_sort Brand, Frank J.
collection PubMed
description BACKGROUND: Interleukin (IL)-1β is involved in the pathology of intervertebral disc degeneration. Under normal conditions, IL-1β is present in cells in an inactive form (pro-IL-1β). However, under pathological conditions, pro-IL-1β is turned into its active form (IL-1β) by the inflammasome, a multi-protein complex of the innate immune response that activates caspase-1. Under conditions of degeneration, the disc experiences an environment of increased acidification. However, the implications of acidification on the innate immune response remain poorly explored. METHODS: Here we have studied how pH changes in human nucleus pulposus cells affect inflammasome activation by immunoblot analysis of protein lysates obtained from nucleus pulposus cells that were exposed to different pH levels in culture. RESULTS: In this study, we have found that in nucleus pulposus cells, with increased acidification, there was a decrease in inflammasome activation consistent with lower levels of active IL-1β. However, this effect at a pH of 6.5, the lowest pH level tested, was abrogated when cells were treated with IL-1β. CONCLUSIONS: Taken together, these findings suggest that the inflammatory response through IL-1β experienced by the human disc is not initiated in nucleus pulposus cells when the stimulus is acidification. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12950-016-0137-0) contains supplementary material, which is available to authorized users.
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spelling pubmed-49977582016-08-26 Acidification changes affect the inflammasome in human nucleus pulposus cells Brand, Frank J. Forouzandeh, Mahtab Kaur, Harmanpreet Travascio, Francesco de Rivero Vaccari, Juan Pablo J Inflamm (Lond) Research BACKGROUND: Interleukin (IL)-1β is involved in the pathology of intervertebral disc degeneration. Under normal conditions, IL-1β is present in cells in an inactive form (pro-IL-1β). However, under pathological conditions, pro-IL-1β is turned into its active form (IL-1β) by the inflammasome, a multi-protein complex of the innate immune response that activates caspase-1. Under conditions of degeneration, the disc experiences an environment of increased acidification. However, the implications of acidification on the innate immune response remain poorly explored. METHODS: Here we have studied how pH changes in human nucleus pulposus cells affect inflammasome activation by immunoblot analysis of protein lysates obtained from nucleus pulposus cells that were exposed to different pH levels in culture. RESULTS: In this study, we have found that in nucleus pulposus cells, with increased acidification, there was a decrease in inflammasome activation consistent with lower levels of active IL-1β. However, this effect at a pH of 6.5, the lowest pH level tested, was abrogated when cells were treated with IL-1β. CONCLUSIONS: Taken together, these findings suggest that the inflammatory response through IL-1β experienced by the human disc is not initiated in nucleus pulposus cells when the stimulus is acidification. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12950-016-0137-0) contains supplementary material, which is available to authorized users. BioMed Central 2016-08-24 /pmc/articles/PMC4997758/ /pubmed/27563282 http://dx.doi.org/10.1186/s12950-016-0137-0 Text en © The Author(s). 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Brand, Frank J.
Forouzandeh, Mahtab
Kaur, Harmanpreet
Travascio, Francesco
de Rivero Vaccari, Juan Pablo
Acidification changes affect the inflammasome in human nucleus pulposus cells
title Acidification changes affect the inflammasome in human nucleus pulposus cells
title_full Acidification changes affect the inflammasome in human nucleus pulposus cells
title_fullStr Acidification changes affect the inflammasome in human nucleus pulposus cells
title_full_unstemmed Acidification changes affect the inflammasome in human nucleus pulposus cells
title_short Acidification changes affect the inflammasome in human nucleus pulposus cells
title_sort acidification changes affect the inflammasome in human nucleus pulposus cells
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4997758/
https://www.ncbi.nlm.nih.gov/pubmed/27563282
http://dx.doi.org/10.1186/s12950-016-0137-0
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