IL-4 enhances hypoxia induced HIF-1alpha protein levels in human transformed intestinal cells

FEBS Lett. 2006 Nov 27;580(27):6399-404. doi: 10.1016/j.febslet.2006.10.053. Epub 2006 Nov 3.

Abstract

Hypoxia-inducible factor-1 (HIF-1) is a transcription factor that mediates the adaptive response to hypoxia. Increasing evidence suggests a crucial role for HIF-1 in immune reactions. Here we investigated the effect of the Th2 type cytokines IL-4 and IL-10 on HIF-1alpha mediated response in normoxia (21% O2) and hypoxia (1% O2). Incubation of human transformed intestinal cells (HT-29) with IL-4 significantly increased HIF-1alpha protein levels during hypoxia but not during normoxia. Mechanisms involved are IL-4 induced up-regulation of HIF-1alpha gene transcription and the PI3K signaling pathway. The increase in hypoxia-induced accumulation of HIF-1alpha protein after IL-4 treatment did not result in up-regulation of HIF-1 DNA-binding activity or HIF-1 dependent gene expression. IL-10 did not affect HIF-1alpha protein levels.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Hypoxia / drug effects
  • Cell Line, Transformed
  • DNA / metabolism
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / biosynthesis*
  • Interleukin-10 / metabolism
  • Interleukin-10 / pharmacology
  • Interleukin-4 / metabolism
  • Interleukin-4 / pharmacology*
  • Intestinal Mucosa / metabolism*
  • Intestines / cytology
  • Phosphatidylinositol 3-Kinases / metabolism
  • Protein Binding / drug effects
  • Signal Transduction / drug effects*
  • Up-Regulation / drug effects*

Substances

  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • IL10 protein, human
  • IL4 protein, human
  • Interleukin-10
  • Interleukin-4
  • DNA
  • Phosphatidylinositol 3-Kinases