Genetic Loss of Murine Pyrin, the Familial Mediterranean Fever Protein, Increases Interleukin-1β Levels
نویسندگان
چکیده
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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متن کاملCentre for Arab Genomic Studies
Description MEFV is the gene responsible for familial Mediterranean fever, an autosomal recessive condition mostly seen in Jews, Armenians, Arabs, and Turks, characterized by recurrent episodes of painful inflammation in the abdomen, chest, and/or joints. The gene expresses itself mostly in peripheral blood leucocytes, particularly in mature granulocytes and their precursors. The expressed prot...
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