Interleukin-1beta increases binding of the iron regulatory protein and the synthesis of ferritin by increasing the labile iron pool. Journal   Biochimica et biophysica acta. Citation   Biochim Biophys Acta. 1497(3):279-88 Publication date   2000 Sep 20 Authors   Piñero DJ Hu J Cook BM Scaduto RC Connor JR Investigators   James R. Connor Jianming Hu Russell C. Scaduto, Jr. Grant agencies   National Institute of Diabetes and Digestive and Kidney Diseases Grants   NIDDK 1DK53430 MeSH headings   Ferritins Interleukin-1 Iron Iron-Sulfur Proteins RNA-Binding Proteins MeSH qualifiers   biosynthesis pharmacology analysis metabolism Abstract   This study was undertaken to begin to elucidate the mechanisms by which cytokines influence intracellular iron homeostasis. Intracellular iron homeostasis is maintained by the coordinated regulation of ferritin and transferrin receptor synthesis. The synthesis of these proteins is coordinated by cytoplasmic iron regulatory proteins (IRP), which bind to iron responsive elements (IRE) on their mRNAs. We evaluated the effects of interleukin-1beta (IL-1beta) on iron metabolism in human astrocytoma cells (SW1088). Exposure to IL-1beta for 16 h increased binding of the IRPs to the IRE and also increased ferritin synthesis. Using the iron sensitive dye calcein, we determined that the intracellular labile iron pool increased within 4 h of IL-1beta exposure and continued to increase for 8 h, returning to normal by 16 h. We propose that the cytokine induced increase in the labile iron pool stimulates ferritin synthesis resulting in a subsequent decrease in the labile iron pool. The decrease in the labile iron pool is consistent with the increase in IRE/IRP interaction measured at 16 h. These results indicate that cytokines can influence the labile iron pool and the post-transcriptional regulatory mechanism for maintaining iron homeostasis. These results contribute to understanding the response of ferritin to inflammation by suggesting ferritin synthesis may reflect changes in the labile iron pool. The approach used in this study may provide a model system for studying relations between the labile iron pool and proteins responsible for maintaining intracellular homeostasis Medline ID   20452588