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

Research output: Contribution to journalArticle

Abstract

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
Volume24
Issue number6
StatePublished - 2001

Fingerprint

Interleukin-13
Up-Regulation
Epithelial Cells
Tumor Necrosis Factor-alpha
Chemical activation
Transcription
Plasmids
STAT6 Transcription Factor
Budesonide
DNA Probes
Nuclear Proteins
Luciferases
Protein Binding
Transcriptional Activation
Glucocorticoids
Proteins
Epithelium
Binding Sites

ASJC Scopus subject areas

  • Cell Biology
  • Pulmonary and Respiratory Medicine
  • Molecular Biology

Cite this

Matsukura, S., Stellato, C., Georas, S. N., Casolaro, V., Plitt, J. R., Miura, K., ... Schleimer, R. P. (2001). Interleukin-13 upregulates eotaxin expression in airway epithelial cells by a STAT6-dependent mechanism. American Journal of Respiratory Cell and Molecular Biology, 24(6), 755-761.

Interleukin-13 upregulates eotaxin expression in airway epithelial cells by a STAT6-dependent mechanism. / Matsukura, S.; Stellato, C.; Georas, S. N.; Casolaro, V.; Plitt, J. R.; Miura, K.; Kurosawa, S.; Schindler, U.; Schleimer, R. P.

In: American Journal of Respiratory Cell and Molecular Biology, Vol. 24, No. 6, 2001, p. 755-761.

Research output: Contribution to journalArticle

Matsukura, S, Stellato, C, Georas, SN, Casolaro, V, Plitt, JR, Miura, K, Kurosawa, S, Schindler, U & Schleimer, RP 2001, 'Interleukin-13 upregulates eotaxin expression in airway epithelial cells by a STAT6-dependent mechanism', American Journal of Respiratory Cell and Molecular Biology, vol. 24, no. 6, pp. 755-761.
Matsukura, S. ; Stellato, C. ; Georas, S. N. ; Casolaro, V. ; Plitt, J. R. ; Miura, K. ; Kurosawa, S. ; Schindler, U. ; Schleimer, R. P. / Interleukin-13 upregulates eotaxin expression in airway epithelial cells by a STAT6-dependent mechanism. In: American Journal of Respiratory Cell and Molecular Biology. 2001 ; Vol. 24, No. 6. pp. 755-761.
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AU - Matsukura, S.

AU - Stellato, C.

AU - Georas, S. N.

AU - Casolaro, V.

AU - Plitt, J. R.

AU - Miura, K.

AU - Kurosawa, S.

AU - Schindler, U.

AU - Schleimer, R. P.

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