Expression of proinflammatory cytokines via HIF-1alpha and NF-kappaB activation on desferrioxamine-stimulated HMC-1 cells

Biochem Biophys Res Commun. 2003 Jul 11;306(4):805-11. doi: 10.1016/s0006-291x(03)01073-8.


We investigated the expression and the role of hypoxia-inducible factor 1alpha (HIF-1alpha) on the desferrioxamine (DFX)-induced cytokine production in human mast cells, HMC-1 cells. HIF-1alpha mRNA was constitutively expressed in mast cell lines including the P815, RBL-2H3, and HMC-1. DFX (100 microM) resulted in a great increase in protein levels of HIF-1alpha in HMC-1 cells, but it did not affect HIF-1alpha mRNA expression. Iron (HIF-1 inhibitor) inhibited increase of HIF-1alpha and NF-kappaB protein levels. Pyrriolidine-dithiocarbamate (PDTC, NF-kappaB inhibitor) inhibited increase of NF-kappaB protein levels, but it slightly increased HIF-1alpha protein levels. In addition, DFX significantly increased the production of IL-6, IL-8, and TNF-alpha in HMC-1 (P<0.05). These increased cytokine levels were significantly inhibited by treatment of iron or PDTC in a dose-dependent manner (P<0.05). We demonstrated the regulatory effects of HIF-1alpha on the DFX-induced proinflammatory cytokine production in human mast cells for the first time. These data indicate that inflammatory cytokines seem to be under HIF-1alpha or NF-kappaB transcriptional regulation in the hypoxic conditions on mast cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Cell Line
  • Cell Nucleus / metabolism
  • Cells, Cultured
  • Cytokines / metabolism
  • Deferoxamine / pharmacology*
  • Dose-Response Relationship, Drug
  • Enzyme Activation
  • Humans
  • Hypoxia
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Interleukin-6 / metabolism
  • Interleukin-8 / metabolism
  • Iron / pharmacology
  • Iron Chelating Agents / pharmacology
  • Mast Cells / cytology
  • NF-kappa B / biosynthesis*
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Time Factors
  • Transcription Factors / biosynthesis*
  • Transcription, Genetic
  • Tumor Necrosis Factor-alpha / metabolism


  • Cytokines
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Interleukin-6
  • Interleukin-8
  • Iron Chelating Agents
  • NF-kappa B
  • RNA, Messenger
  • Transcription Factors
  • Tumor Necrosis Factor-alpha
  • Iron
  • Deferoxamine