Manuel A Fernandez-Rojo, Michael A Pearen, Anita G Burgess, Maria P Ikonomopoulou, Diem Hoang-Le, Berit Genz, Silvia L Saggiomo, Sujeevi S K Nawaratna, Maura Poli, Regina Reissmann, Geoffrey N Gobert, Urban Deutsch, Britta Engelhardt, Andrew J Brooks, Alun Jones, Paolo Arosio, Grant A Ramm
Serum ferritin concentrations increase during hepatic inflammation and correlate with the severity of chronic liver disease. Here, we report a molecular mechanism whereby the heavy subunit of ferritin (FTH) contributes to hepatic inflammation. We found that FTH induced activation of the NLRP3 inflammasome and secretion of the proinflammatory cytokine interleukin-1β (IL-1β) in primary rat hepatic stellate cells (HSCs) through intercellular adhesion molecule-1 (ICAM-1). FTH-ICAM-1 stimulated the expression of Il1b , NLRP3 inflammasome activation, and the processing and secretion of IL-1β in a manner that depended on plasma membrane remodeling, clathrin-mediated endocytosis, and lysosomal destabilization...
April 2, 2024: Science Signaling