Interleukin-1β increases binding of the iron regulatory protein and the synthesis of ferritin by increasing the labile iron pool

Domingo J. Piñero, Jing Hu, Braden M. Cook, Russell Scaduto, James Connor

Research output: Contribution to journalArticle

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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-1β (IL-1β) on iron metabolism in human astrocytoma cells (SW1088). Exposure to IL-1β for 16 h increased binding of the IRPs to the IRE and also increased ferritin synthesis. Using the iron sensitive dye calcine, we determined that the intracellular labile iron pool increased within 4 h of IL-1β 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. (C) 2000 Elsevier Science B.V.

Original languageEnglish (US)
Pages (from-to)279-288
Number of pages10
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1497
Issue number3
DOIs
StatePublished - Sep 20 2000

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Iron-Regulatory Proteins
Ferritins
Interleukin-1
Iron
Homeostasis
Cytokines
Interleukin-16
Transferrin Receptors

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

Cite this

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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-1β (IL-1β) on iron metabolism in human astrocytoma cells (SW1088). Exposure to IL-1β for 16 h increased binding of the IRPs to the IRE and also increased ferritin synthesis. Using the iron sensitive dye calcine, we determined that the intracellular labile iron pool increased within 4 h of IL-1β 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. (C) 2000 Elsevier Science B.V.",
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Interleukin-1β increases binding of the iron regulatory protein and the synthesis of ferritin by increasing the labile iron pool. / Piñero, Domingo J.; Hu, Jing; Cook, Braden M.; Scaduto, Russell; Connor, James.

In: Biochimica et Biophysica Acta - Molecular Cell Research, Vol. 1497, No. 3, 20.09.2000, p. 279-288.

Research output: Contribution to journalArticle

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AU - Piñero, Domingo J.

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AU - Connor, James

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