Interleukin-1 beta induces ceruloplasmin and ferroportin-1 gene expression via MAP kinases and C/EBP beta, AP-1, and NF-kB activation

Previously, we demonstrated that IL-1 beta was able to increase iron efflux from glial cells through a coordinate induction of both ferroportin-1 (Fpn) and ceruloplasmin (Cp) synthesis. In this study, we have investigated the signaling pathways that are involved in the transcriptional activation of the Cp and Fpn. Our data show that the expression of Cp and Fpn in response to IL-1 beta requires the activation of MAP kinase pathways as a consequence of an IL-1 beta receptor stimulation. Moreover, we have observed that IL-1 beta regulates the expression of Cp and Fpn genes through (i) p38 MAPK-mediated activation of C/EBP transcription factor, (ii) ERK1/2-, JNK1- and partially p38 MAPK-dependent activation of AP-1, and through (iii) activation of NF-kappa B partially mediated by p38 MAPK. (C) 2010 Elsevier Ireland Ltd. All rights reserved.