TNF-alpha and IL-4 regulate expression of IL-13 receptor alpha2 on human fibroblasts

Biochem Biophys Res Commun. 2003 Dec 26;312(4):1248-55. doi: 10.1016/j.bbrc.2003.11.077.


Two interleukin 13 receptors (IL-13Rs) have been identified as IL-13Ralpha1 and IL-13Ralpha2. IL-13Ralpha1 is composed of a heterodimer consisting of IL-13Ralpha1 and IL-4 receptor alpha (IL-4Ralpha) as a signaling subunit. In contrast, IL-13Ralpha2 is known as a decoy receptor for IL-13. In this study, we investigated the expression of IL-13Rs on human fibroblasts. IL-13Ralpha2 was significantly up-regulated after stimulation with tumor necrosis factor-alpha (TNF-alpha) and/or IL-4. In contrast, IL-13Ralpha1 was constitutively detectable and was not up-regulated. After the induction of IL-13alpha2 by IL-4, STAT6 phosphorylation through IL-13Ralpha1 by IL-13 was inhibited. We also detected large intracellular pools of IL-13Ralpha2 in fibroblasts quantitatively. Furthermore, mobilization of the IL-13Ralpha2 protein stores from the cytoplasm to the cell surface was prevented by an inhibitor of protein transport, brefeldin-A. These results indicate that TNF-alpha and IL-4 synergistically up-regulate the expression of IL-13Ralpha2 decoy receptor on human fibroblasts by inducing gene expression and mobilizing intracellular receptors, and thus may down-regulate the IL-13 signaling.

Publication types

  • Comparative Study

MeSH terms

  • Cell Line
  • Cells, Cultured
  • Fibroblasts / classification
  • Fibroblasts / metabolism*
  • Gene Expression Regulation*
  • Humans
  • Interleukin-13 Receptor alpha1 Subunit
  • Interleukin-4 / metabolism*
  • Lung / metabolism*
  • Nasal Polyps / metabolism*
  • Organ Specificity
  • Receptors, Interleukin / metabolism*
  • Receptors, Interleukin-13
  • Receptors, Interleukin-4 / metabolism
  • Signal Transduction
  • Skin / metabolism*
  • Tumor Necrosis Factor-alpha / metabolism*


  • IL13RA1 protein, human
  • Interleukin-13 Receptor alpha1 Subunit
  • Receptors, Interleukin
  • Receptors, Interleukin-13
  • Receptors, Interleukin-4
  • Tumor Necrosis Factor-alpha
  • Interleukin-4