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Genetic Loss of Murine Pyrin, the Familial Mediterranean Fever Protein, Increases Interleukin-1β Levels

Familial Mediterranean Fever (FMF) is an inherited autoinflammatory disorder characterized by unprovoked episodes of fever and inflammation. The associated gene, MEFV (Mediterranean Fever), is expressed primarily by cells of myeloid lineage and encodes the protein pyrin/TRIM20/Marenostrin. The mecha...

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Autores principales: Hesker, Pamela R., Nguyen, MyTrang, Kovarova, Martina, Ting, Jenny P.-Y., Koller, Beverly H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3511413/
https://www.ncbi.nlm.nih.gov/pubmed/23226472
http://dx.doi.org/10.1371/journal.pone.0051105
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author Hesker, Pamela R.
Nguyen, MyTrang
Kovarova, Martina
Ting, Jenny P.-Y.
Koller, Beverly H.
author_facet Hesker, Pamela R.
Nguyen, MyTrang
Kovarova, Martina
Ting, Jenny P.-Y.
Koller, Beverly H.
author_sort Hesker, Pamela R.
collection PubMed
description Familial Mediterranean Fever (FMF) is an inherited autoinflammatory disorder characterized by unprovoked episodes of fever and inflammation. The associated gene, MEFV (Mediterranean Fever), is expressed primarily by cells of myeloid lineage and encodes the protein pyrin/TRIM20/Marenostrin. The mechanism by which mutations in pyrin alter protein function to cause episodic inflammation is controversial. To address this question, we have generated a mouse line lacking the Mefv gene by removing a 21 kb fragment containing the entire Mefv locus. While the development of immune cell populations appears normal in these animals, we show enhanced interleukin (IL) 1β release by Mefv (−/−) macrophages in response to a spectrum of inflammatory stimuli, including stimuli dependent on IL-1β processing by the NLRP1b, NLRP3 and NLRC4 inflammasomes. Caspase-1 activity, however, did not change under identical conditions. These results are consistent with a model in which pyrin acts to limit the release of IL-1β generated by activation and assembly of inflammasomes in response to subclinical immune challenges.
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spelling pubmed-35114132012-12-05 Genetic Loss of Murine Pyrin, the Familial Mediterranean Fever Protein, Increases Interleukin-1β Levels Hesker, Pamela R. Nguyen, MyTrang Kovarova, Martina Ting, Jenny P.-Y. Koller, Beverly H. PLoS One Research Article Familial Mediterranean Fever (FMF) is an inherited autoinflammatory disorder characterized by unprovoked episodes of fever and inflammation. The associated gene, MEFV (Mediterranean Fever), is expressed primarily by cells of myeloid lineage and encodes the protein pyrin/TRIM20/Marenostrin. The mechanism by which mutations in pyrin alter protein function to cause episodic inflammation is controversial. To address this question, we have generated a mouse line lacking the Mefv gene by removing a 21 kb fragment containing the entire Mefv locus. While the development of immune cell populations appears normal in these animals, we show enhanced interleukin (IL) 1β release by Mefv (−/−) macrophages in response to a spectrum of inflammatory stimuli, including stimuli dependent on IL-1β processing by the NLRP1b, NLRP3 and NLRC4 inflammasomes. Caspase-1 activity, however, did not change under identical conditions. These results are consistent with a model in which pyrin acts to limit the release of IL-1β generated by activation and assembly of inflammasomes in response to subclinical immune challenges. Public Library of Science 2012-11-30 /pmc/articles/PMC3511413/ /pubmed/23226472 http://dx.doi.org/10.1371/journal.pone.0051105 Text en © 2012 Hesker et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Hesker, Pamela R.
Nguyen, MyTrang
Kovarova, Martina
Ting, Jenny P.-Y.
Koller, Beverly H.
Genetic Loss of Murine Pyrin, the Familial Mediterranean Fever Protein, Increases Interleukin-1β Levels
title Genetic Loss of Murine Pyrin, the Familial Mediterranean Fever Protein, Increases Interleukin-1β Levels
title_full Genetic Loss of Murine Pyrin, the Familial Mediterranean Fever Protein, Increases Interleukin-1β Levels
title_fullStr Genetic Loss of Murine Pyrin, the Familial Mediterranean Fever Protein, Increases Interleukin-1β Levels
title_full_unstemmed Genetic Loss of Murine Pyrin, the Familial Mediterranean Fever Protein, Increases Interleukin-1β Levels
title_short Genetic Loss of Murine Pyrin, the Familial Mediterranean Fever Protein, Increases Interleukin-1β Levels
title_sort genetic loss of murine pyrin, the familial mediterranean fever protein, increases interleukin-1β levels
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3511413/
https://www.ncbi.nlm.nih.gov/pubmed/23226472
http://dx.doi.org/10.1371/journal.pone.0051105
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