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 language | English (US) |
|---|---|
| Pages (from-to) | 755-761 |
| Number of pages | 7 |
| Journal | American Journal of Respiratory Cell and Molecular Biology |
| Volume | 24 |
| Issue number | 6 |
| State | Published - 2001 |
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ASJC Scopus subject areas
- Cell Biology
- Pulmonary and Respiratory Medicine
- Molecular Biology
Cite this
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 journal › Article
}
TY - JOUR
T1 - Interleukin-13 upregulates eotaxin expression in airway epithelial cells by a STAT6-dependent mechanism
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.
PY - 2001
Y1 - 2001
N2 - 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.
AB - 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.
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M3 - Article
C2 - 11415942
AN - SCOPUS:0034976854
VL - 24
SP - 755
EP - 761
JO - American Journal of Respiratory Cell and Molecular Biology
JF - American Journal of Respiratory Cell and Molecular Biology
SN - 1044-1549
IS - 6
ER -