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

S. Matsukura, C. Stellato, S. N. Georas, V. Casolaro, J. R. Plitt, K. Miura, S. Kurosawa, U. Schindler, R. P. Schleimer*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

157 Scopus citations


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)-α and also was inhibited by the glucocorticoid budesonide. To establish the mechanisms of eotaxin up-regulation 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-α (2.8-fold). The combination of IL-13 and TNF-α 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-α 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.

Original languageEnglish (US)
Pages (from-to)755-761
Number of pages7
JournalAmerican journal of respiratory cell and molecular biology
Issue number6
StatePublished - 2001

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology


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