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Release of Interleukin-1α or Interleukin-1β Depends on Mechanism of Cell Death
The cytokine interleukin-1 (IL-1) has two main pro-inflammatory forms, IL-1α and IL-1β, which are central to host responses to infection and to damaging sterile inflammation. Processing of IL-1 precursor proteins to active cytokines commonly occurs through activation of proteases, notably caspases a...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Biochemistry and Molecular Biology
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4047367/ https://www.ncbi.nlm.nih.gov/pubmed/24790078 http://dx.doi.org/10.1074/jbc.M114.557561 |
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author | England, Hazel Summersgill, Holly R. Edye, Michelle E. Rothwell, Nancy J. Brough, David |
author_facet | England, Hazel Summersgill, Holly R. Edye, Michelle E. Rothwell, Nancy J. Brough, David |
author_sort | England, Hazel |
collection | PubMed |
description | The cytokine interleukin-1 (IL-1) has two main pro-inflammatory forms, IL-1α and IL-1β, which are central to host responses to infection and to damaging sterile inflammation. Processing of IL-1 precursor proteins to active cytokines commonly occurs through activation of proteases, notably caspases and calpains. These proteases are instrumental in cell death, and inflammation and cell death are closely associated, hence we sought to determine the impact of cell death pathways on IL-1 processing and release. We discovered that apoptotic regulation of caspase-8 specifically induced the processing and release of IL-1β. Conversely, necroptosis caused the processing and release of IL-1α, and this was independent of IL-1β processing and release. These data suggest that the mechanism through which an IL-1-expressing cell dies dictates the nature of the inflammatory mechanism that follows. These insights may allow modification of inflammation through the selective targeting of cell death mechanisms during disease. |
format | Online Article Text |
id | pubmed-4047367 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | American Society for Biochemistry and Molecular Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-40473672014-06-11 Release of Interleukin-1α or Interleukin-1β Depends on Mechanism of Cell Death England, Hazel Summersgill, Holly R. Edye, Michelle E. Rothwell, Nancy J. Brough, David J Biol Chem Immunology The cytokine interleukin-1 (IL-1) has two main pro-inflammatory forms, IL-1α and IL-1β, which are central to host responses to infection and to damaging sterile inflammation. Processing of IL-1 precursor proteins to active cytokines commonly occurs through activation of proteases, notably caspases and calpains. These proteases are instrumental in cell death, and inflammation and cell death are closely associated, hence we sought to determine the impact of cell death pathways on IL-1 processing and release. We discovered that apoptotic regulation of caspase-8 specifically induced the processing and release of IL-1β. Conversely, necroptosis caused the processing and release of IL-1α, and this was independent of IL-1β processing and release. These data suggest that the mechanism through which an IL-1-expressing cell dies dictates the nature of the inflammatory mechanism that follows. These insights may allow modification of inflammation through the selective targeting of cell death mechanisms during disease. American Society for Biochemistry and Molecular Biology 2014-06-06 2014-04-30 /pmc/articles/PMC4047367/ /pubmed/24790078 http://dx.doi.org/10.1074/jbc.M114.557561 Text en © 2014 by The American Society for Biochemistry and Molecular Biology, Inc. Author's Choice—Final version full access. Creative Commons Attribution Unported License (http://creativecommons.org/licenses/by/3.0/) applies to Author Choice Articles |
spellingShingle | Immunology England, Hazel Summersgill, Holly R. Edye, Michelle E. Rothwell, Nancy J. Brough, David Release of Interleukin-1α or Interleukin-1β Depends on Mechanism of Cell Death |
title | Release of Interleukin-1α or Interleukin-1β Depends on Mechanism of Cell Death |
title_full | Release of Interleukin-1α or Interleukin-1β Depends on Mechanism of Cell Death |
title_fullStr | Release of Interleukin-1α or Interleukin-1β Depends on Mechanism of Cell Death |
title_full_unstemmed | Release of Interleukin-1α or Interleukin-1β Depends on Mechanism of Cell Death |
title_short | Release of Interleukin-1α or Interleukin-1β Depends on Mechanism of Cell Death |
title_sort | release of interleukin-1α or interleukin-1β depends on mechanism of cell death |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4047367/ https://www.ncbi.nlm.nih.gov/pubmed/24790078 http://dx.doi.org/10.1074/jbc.M114.557561 |
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