Ferritin induces IL-1β production through inflammasome activation via NF-κB-dependent manner in macrophages (835.3)

Ferritin (Ftn), an iron-storage protein, is widely used as an indicator of body iron storage. Serum ferritin was upregulated under the inflammatory status. Recently, the secreted Ftn exerts certain biological actions, however, it remains unclear whether the secreted Ftn itself promotes inflammation. Here, we investigated the biological action of Ftn on inflammation. Murine peritoneal ascites-derived macrophage, RAW264.7, was used in this study. Exogenous Ftn treatment as well as iron-free Apo-Ftn induced IL-1s expression and maturation in macrophage, resulting in increased IL-1s secretion in the supernatant. Ftn and Apo-Ftn promoted caspase-1 activation and upregulated the expression of nucleotide-binding oligomerization domain (NOD)-like receptor family, pyrin domain-containing 3 (NLRP3), inflammasome activation. Ftn-induced IL-1s activation and secretion were inhibited by caspase-1 inhibitor or NLRP3 silencing. Ftn-induced inflammasome activation was independent of iron content and inhibited by the phar...