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- W2002511600 abstract "Familial Mediterranean fever (FMF) is a hereditary recurrent fever associated with mutations in the gene MEFV encoding pyrin. It is expressed mainly in neutrophils and macrophages, and modulates the production of the potent pro-inflammatory cytokine interleukin-1β through regulation of nuclear factor-κB and caspase-1. The MEFV gene expression depends on multiple levels of regulation. Sequence variants located in the promoter and at the 3'-untranslated region of the gene modulate this expression. Two studies demonstrated decreased mRNA levels in FMF patients compared with healthy subjects, whereas two others found no significant differences. The diverse experimental settings may have resulted in variable quantification of the 15 splice variants that have been identified recently. Some of these isoforms are regulated by nonsense-mediated decay in both cell- and transcript-specific manner, and may be differentially translated in THP1 cells. In addition, pyrin may be cleaved by caspase 1. The full-length pyrin was less abundant than the cleaved fragment in mononuclear cells from FMF patients than in controls, whereas the opposite was observed in granulocytes. Altogether, the regulation of MEFV expression is more complex than anticipated in both physiological and pathological conditions. Its deregulation is likely to alter the inflammasome function and subsequently result in uncontrolled inflammation as seen in FMF." @default.
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- W2002511600 date "2011-07-21" @default.
- W2002511600 modified "2023-10-05" @default.
- W2002511600 title "The regulation of MEFV expression and its role in health and familial Mediterranean fever" @default.
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- W2002511600 doi "https://doi.org/10.1038/gene.2011.53" @default.
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