Translational control during the acute phase response. Ferritin synthesis in response to interleukin-1.
Interleukin-1 (IL-1 beta) increases the synthesis of both heavy and light (L)-ferritin subunits when added to human hepatoma cells (HepG2) grown in culture. RNase protection and Northern blot analysis with L-ferritin probes revealed that no changes in L-ferritin mRNA levels occur after cytokine stimulation. However, the induction coincides with an increased association of the L-subunit mRNA with polyribosomes. Since the recruitment of stored ferritin mRNA onto polyribosomes is seen when iron enters the cell, the effect of IL-1 beta on iron uptake was tested and was found to be unaffected by the lymphokine. Neither transferrin receptor mRNA levels nor the number of receptors displayed on the cell surface was affected by IL-1 beta. However, the action of the cytokine on ferritin translation is inhibited by the action of the intracellular iron chelator deferoxamine. These data indicate that IL-1 beta induces ferritin gene expression by translational control of its mRNA. The pathway of induction is different from iron-dependent ferritin gene expression whereas regulation requires the background presence of cellular iron.
Division of Hematology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115.
J T
JT
Rogers
K R
KR
Bridges
G P
GP
Durmowicz
J
J
Glass
P E
PE
Auron
H N
HN
Munro
D000209:Acute-Phase Proteins / Q000096:biosynthesis / Q000235:genetics*; D001692:Biological Transport; D006528:Carcinoma, Hepatocellular; D002460:Cell Line; D003676:Deferoxamine / Q000494:pharmacology; D005293:Ferritins / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D007501:Iron / Q000378:metabolism / Q000494:pharmacology; D008099:Liver / Q000378:metabolism; D008113:Liver Neoplasms; D046911:Macromolecular Substances; D009693:Nucleic Acid Hybridization; D011132:Polyribosomes / Q000378:metabolism; D014176:Protein Biosynthesis / Q000187:drug effects*; D012333:RNA, Messenger / Q000235:genetics / Q000302:isolation & purification; D012334:RNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D011994:Recombinant Proteins / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D000209:Acute-Phase Proteins; D007375:Interleukin-1; D046911:Macromolecular Substances; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011994:Recombinant Proteins; D005293:Ferritins; D007501:Iron; D003676:Deferoxamine