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Publication : Genetic loss of murine pyrin, the Familial Mediterranean Fever protein, increases interleukin-1β levels.

First Author  Hesker PR Year  2012
Journal  PLoS One Volume  7
Issue  11 Pages  e51105
PubMed ID  23226472 Mgi Jnum  J:192443
Mgi Id  MGI:5465110 Doi  10.1371/journal.pone.0051105
Citation  Hesker PR, et al. (2012) Genetic loss of murine pyrin, the Familial Mediterranean Fever protein, increases interleukin-1beta levels. PLoS One 7(11):e51105
abstractText  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) 1beta release by Mefv(-/-) macrophages in response to a spectrum of inflammatory stimuli, including stimuli dependent on IL-1beta 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-1beta generated by activation and assembly of inflammasomes in response to subclinical immune challenges.
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