Molecular mechanisms of repression of eotaxin expression with fluticasone propionate in airway epithelial cells

Satoshi Matsukura*, Fumio Kokubu, Masatsugu Kurokawa, Mio Kawaguchi, Hideki Kuga, Koushi Ieki, Miho Odaka, Shintaro Suzuki, Shin Watanabe, Hiroko Takeuchi, Robert P. Schleimer, Ulrike Schindler, Mitsuru Adachi

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


Background: Glucocorticoids are known to repress the expression of CC chemokine eotaxin in airway epithelial cells. We focused our study on the molecular mechanisms of the glucocorticoid, fluticasone, in the inhibition of the expression of the eotaxin gene in the cells. Methods: The airway epithelial cell line, BEAS-2B, was stably transfected with signal transducers and activators of transcription 6 (STAT6)-expressing vector and used in the following experiments to clarify the function of STAT6. Levels of eotaxin mRNA and protein expression were determined with RT-PCR and ELISA. Mechanisms of transcriptional regulation were assessed by the electrophoretic mobility shift assay and dual luciferase assay using eotaxin promoter-luciferase reporter plasmids. Results: Fluticasone significantly inhibited the induction of eotaxin protein stimulated with TNF-α and IL-4 in the cells. Fluticasone also repressed the induction of eotaxin mRNA with these stimuli. It partially inhibited the activity of eotaxin promoter; however, it did not inhibit the nuclear translocation and binding of transcription factors, nuclear factor-kappa B (NF-κB) or STAT6, to the DNA derived from the proximal promoter region of the eotaxin gene. Moreover, the inhibitory effect was also conserved in the experiments using the reporter plasmid of which the putative glucocorticoid-responsive element was mutated. Conclusions: Fluticasone inhibits the expression of eotaxin gene in airway epithelial cells in part through repression of the transcription. However, the mechanisms depend neither on the inhibition of transcription factors' translocation into nuclei nor the function of the putative glucocorticoid-responsive element in the promoter, indicating that other mechanisms would be related to the transcriptional repression of the eotaxin gene in airway epithelial cells.

Original languageEnglish (US)
Pages (from-to)12-20
Number of pages9
JournalInternational archives of allergy and immunology
Issue numberSUPPL. 1
StatePublished - Jun 15 2004


  • Airway epithelial cells
  • Asthma
  • Eotaxin
  • Fluticasone
  • Glucocorticoid
  • Nuclear factor-kappa B
  • Signal transducers and activators of transcription 6

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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