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IL-4 Induces Mucin Gene Expression and Goblet Cell Metaplasia In Vitro and In Vivo

Karim Dabbagh, Kiyoshi Takeyama, Heung-Man Lee, Iris F. Ueki, James A. Lausier and Jay A. Nadel
J Immunol May 15, 1999, 162 (10) 6233-6237;
Karim Dabbagh
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Kiyoshi Takeyama
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Heung-Man Lee
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Iris F. Ueki
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James A. Lausier
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Jay A. Nadel
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    FIGURE 1.

    IL-4R expression in NCI-H292 cells. Immunocytochemical analysis of IL-4R α-chain in NCI-H292 cells. All cells displayed a positive signal for the IL-4R α-chain, although the staining was more intense in areas of dense confluence (left panel, arrows). Cells incubated with isotype control Ab were negative (right panel). Results are representative of three separate experiments. Bar = 25 μm.

  •   FIGURE 2.
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    FIGURE 2.

    Effect of IL-4 on mucous glycoconjugate production in NCI-H292 cells. Densitometric analysis of PAS-positive material produced by NCI-H292 cells in response to control and IL-4-supplemented medium (10 ng/ml) at 24, 48, and 72 h. Cell culture supernatant (secreted mucous glycoconjugates, solid bars) and cell lysates (intracellular mucous glycoconjugates, open bars) were blotted onto nitrocellulose membranes and stained with PAS. IL-4 increased the amount of both intracellular and secreted mucous glycoconjugates, which was greatest at 72 h. The figure is representative of three separate experiments (n = 4; ∗, p < 0.05 compared with control). Bars are the mean ± SEM. C, control.

  •   FIGURE 3.
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    FIGURE 3.

    Effect of IL-4 on MUC2 gene expression in NCI-H292 cells. AB/PAS staining (top panels) and in situ hybridization for the MUC2 gene (bottom panels) in NCI-H292 cells treated with control medium (left panels) or IL-4-supplemented medium (10 ng/ml; right panels) for 24 h. NCI-H292 cells displayed basal PAS staining and MUC2 gene expression. IL-4 treatment increased the number and intensity of cells staining positively for PAS (arrows) and increased MUC2 gene expression. The figure shows representative results from three different experiments. Bar = 25 μm.

  •   FIGURE 4.
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    FIGURE 4.

    IL-4R protein expression in mouse airway epithelium. When the tissue was stained with an anti-IL-4Rα Ab, most airway epithelial cells stained positively (upper panel); sections incubated with isotype control Ab remained unstained (lower panel). Bar = 25 μm.

  •   FIGURE 5.
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    FIGURE 5.

    Effects of IL-4 on AB/PAS staining (top panels) and MUC5AC gene expression (bottom panels) in mice at 24 h. In control mice (left panels) AB/PAS staining was low, and MUC5AC staining was not visible. Airway instillation of IL-4 (250 ng) increased AB/PAS staining and MUC5AC gene expression; expression colocalized with AB/PAS staining. Bar = 25 μm.

  •   FIGURE 6.
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    FIGURE 6.

    Effect of IL-4 on goblet cell area in bronchial epithelium in vivo. Semiquantitative analysis of relative AB/PAS-positive staining area in the airways of mice treated with PBS (control) or IL-4 (250 ng) for 24 h. IL-4 increased the percentage of area stained with AB/PAS (n = 5; p < 0.05) at 24 h. Bars are the mean ± SEM.

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The Journal of Immunology: 162 (10)
The Journal of Immunology
Vol. 162, Issue 10
15 May 1999
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IL-4 Induces Mucin Gene Expression and Goblet Cell Metaplasia In Vitro and In Vivo
Karim Dabbagh, Kiyoshi Takeyama, Heung-Man Lee, Iris F. Ueki, James A. Lausier, Jay A. Nadel
The Journal of Immunology May 15, 1999, 162 (10) 6233-6237;

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IL-4 Induces Mucin Gene Expression and Goblet Cell Metaplasia In Vitro and In Vivo
Karim Dabbagh, Kiyoshi Takeyama, Heung-Man Lee, Iris F. Ueki, James A. Lausier, Jay A. Nadel
The Journal of Immunology May 15, 1999, 162 (10) 6233-6237;
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