Selective induction of eotaxin release by interleukin-13 or interleukin-4 in human airway smooth muscle cells is synergistic with interleukin-1beta and is mediated by the interleukin-4 receptor alpha-chain

Am J Respir Crit Care Med. 2002 Apr 15;165(8):1161-71. doi: 10.1164/ajrccm.165.8.2107158.


The biologic activities of interleukin (IL)-13 and IL-4 often overlap, and evidence supports their importance in atopic disease and airways hyperresponsiveness. Here, their capacity to release eosinophil-activating cytokines was examined in cultured human airway smooth muscle. IL-13 and IL-4 induced selective release of eotaxin with no effect on granulocyte-macrophage colony-stimulating factor, regulated upon activation, normal T-cell expressed and secreted (RANTES), or IL-8. A profound synergistic increase in eotaxin release occurred when IL-13 or IL-4 was combined with IL-1beta that was abrogated by a neutralizing antibody to the IL-4 receptor alpha (IL-4Ralpha)-chain but not to the IL-2 receptor gamma (IL-2Rgamma)-chain. Expression of cell surface IL-4 receptors and IL-4Ralpha in lysates was constitutive and unchanged by treatment with IL-13 or IL-4 alone or in combination with IL-1beta. Activation of IL-4Ralpha by IL-13 or IL-4 induced signal transducer and activation of transcription-6 (STAT6), p42/ p44 ERK, p38, and to a lesser extent, SAPK/JNK mitogen-activated protein kinase phosphorylation. STAT6 and MAP kinase activation by IL-13 or IL-4 was not further potentiated after combined stimulation with IL-1beta. However, eotaxin release induced by IL-13 or IL-4 alone, and in combination with IL-1beta, was prevented by the MEK inhibitor U 0126 and by the p38 inhibitor SB 202190. Collectively, the data suggest that selective eotaxin release induced either by IL-13 and IL-4 or when combined with IL-1beta is mediated by a constitutive cell surface IL-4Ralpha and the activation of multiple intracellular pathways.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal / pharmacology
  • Bronchi / metabolism*
  • Cells, Cultured
  • Chemokine CCL11
  • Chemokine CCL5 / metabolism
  • Chemokines, CC / metabolism*
  • Chemotactic Factors, Eosinophil / metabolism*
  • Enzyme Activation
  • Female
  • Granulocyte-Macrophage Colony-Stimulating Factor / metabolism
  • Humans
  • Interleukin-1 / physiology
  • Interleukin-13 / physiology
  • Interleukin-4 / physiology
  • Interleukins / physiology*
  • Male
  • Middle Aged
  • Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • Mitogen-Activated Protein Kinases / metabolism
  • Muscle, Smooth / metabolism*
  • Receptors, Interleukin-4 / immunology
  • Receptors, Interleukin-4 / physiology
  • STAT6 Transcription Factor
  • Signal Transduction
  • Trans-Activators / metabolism


  • Antibodies, Monoclonal
  • CCL11 protein, human
  • Chemokine CCL11
  • Chemokine CCL5
  • Chemokines, CC
  • Chemotactic Factors, Eosinophil
  • Interleukin-1
  • Interleukin-13
  • Interleukins
  • Receptors, Interleukin-4
  • STAT6 Transcription Factor
  • STAT6 protein, human
  • Trans-Activators
  • Interleukin-4
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Mitogen-Activated Protein Kinases