Interleukin-13 upregulates eotaxin expression in airway epithelial cells by a STAT6-dependent mechanism

Am J Respir Cell Mol Biol. 2001 Jun;24(6):755-61. doi: 10.1165/ajrcmb.24.6.4351.


Interleukin (IL)-13 is a T helper 2-derived cytokine that has recently been implicated in allergic airway responses. We hypothesized that IL-13 may regulate expression of eotaxin in airway epithelium. We found that IL-13 upregulated eotaxin messenger RNA and protein synthesis in the airway epithelial cell line BEAS-2B; this effect showed synergy with tumor necrosis factor (TNF)-alpha and also was inhibited by the glucocorticoid budesonide. To establish the mechanisms of eotaxin upregulation by IL-13, cells were transfected with an eotaxin promoter-luciferase reporter plasmid and transcription was activated by IL-13 (1.7-fold) and TNF-alpha (2.8-fold). The combination of IL-13 and TNF-alpha additively activated the promoter constructs (4.1-fold). Activation of signal transducer and activator of transcription (STAT) 6 by IL-13 was confirmed by nuclear protein binding to a DNA probe derived from the eotaxin promoter. Activation of eotaxin transcription by IL-13 and the additive effect with TNF-alpha were lost in plasmids mutated at a putative STAT6 binding site. Cotransfection with a wild-type STAT6 expression vector significantly enhanced activation of the eotaxin promoter after IL-13 stimulation (6-fold induction). A significant increase of eotaxin protein secretion in the supernatant of STAT6 wild-type-transfected cells was observed after IL-13 stimulation. Cotransfection with a dominant negative STAT6 mutant expression vector inhibited activation of the eotaxin promoter by IL-13. These results indicate that IL-13 stimulates eotaxin expression in airway epithelial cells and that STAT6 plays a pivotal role in this response.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Cell Line, Transformed
  • Chemokine CCL11
  • Chemokines, CC*
  • Cytokines / biosynthesis*
  • Cytokines / genetics
  • Humans
  • Interleukin-13 / pharmacology*
  • Promoter Regions, Genetic
  • RNA, Messenger / biosynthesis
  • Respiratory Mucosa / cytology
  • Respiratory Mucosa / drug effects
  • Respiratory Mucosa / metabolism*
  • STAT6 Transcription Factor
  • Signal Transduction
  • Trans-Activators / metabolism*
  • Transcriptional Activation
  • Up-Regulation


  • CCL11 protein, human
  • Chemokine CCL11
  • Chemokines, CC
  • Cytokines
  • Interleukin-13
  • RNA, Messenger
  • STAT6 Transcription Factor
  • STAT6 protein, human
  • Trans-Activators