Suplatast tosilate inhibits goblet-cell metaplasia of airway epithelium in sensitized mice

Jae Jeong Shim, Karim Dabbagh, Kiyoshi Takeyama, Pierre Regis Burgel, Trang P. Dao-Pick, Iris F. Ueki, Jay A. Nadel

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Background: IL-4 and IL-13 play a putative role in mucus hypersecretion in asthma. Suplatast tosilate prevents the synthesis of T(H2) cytokines. Objective: Because suplatast tosilate inhibits T(H2) cytokines but does not inhibits IFN-γ production, we examined the effect of suplatast on IL-4- or IL-13- and ovalbumin (OVA)-induced mucin synthesis in NCI-H292 cells in vitro and in bronchi of pathogen-free BALB/c mice in vivo. Methods: In vitro, NCI- H292 cells were preincubated with suplatast tosilate (0.1-100 μg/mL) 1 hour before adding human recombinant IL-4 (10 ng/mL). In vivo, mouse recombinant IL-4 or IL-13 (250 ng per/mouse) was instilled intranasally in mice pretreated with suplatast tosilate (50 mg · kg-1 · d-1). Mucous glycoconjugates were stained with Alcian blue (AB)/periodic acid-Schiff (PAS) stain. To evaluate effects of suplatast tosilate on goblet-cell metaplasia in OVA-sensitized mice, animals were pretreated with suplatast tosilate (1-50 mg · kg-1 · d-1) intragastrically. IL-4 and IL-13 were measured, and allergic inflammatory cells were analyzed in bronchoalveolar lavage fluid of OVA-sensitized mice. Results: Pretreatment with suplastast did not prevent IL-4- or IL-13-induced increase in mucous glycoconjugate production in NCI- H292 cells or in mice. OVA sensitization increased AB/PAS-stained area of the epithelium (48.1% ± 2.4%, P < .01 compared with control mice). Suplatast tosilate inhibited OVA-induced goblet-cell metaplasia in airway epithelium in a dose-dependent fashion; 50 mg · kg-1 · d-1 decreased the AB/PAS area to 22.7% ± 2.7% (P < .05 compared with OVA sensitization alone). Pre- treatment with suplatast tosilate also prevented OVA-induced increase in IL-4 and IL-13 levels and decreased the number of lymphocytes and eosinophils in bronchoalveolar lavage fluid (P < .05 compared with values of mice given OVA alone). Conclusion: These results indicate that suplatast tosilate prevents allergen-induced goblet-cell metaplasia and the recruitment of eosinophils and lymphocytes into the airways. These results suggest that this effect is due to the prevention of the production of T(H2) cytokines in airways.

Original languageEnglish
Pages (from-to)739-745
Number of pages7
JournalJournal of Allergy and Clinical Immunology
Volume105
Issue number4
DOIs
Publication statusPublished - 2000 Jan 1
Externally publishedYes

Fingerprint

Goblet Cells
Metaplasia
Ovalbumin
Interleukin-13
Epithelium
Interleukin-4
Alcian Blue
Periodic Acid
Glycoconjugates
Bronchoalveolar Lavage Fluid
Cytokines
Eosinophils
suplatast tosilate
Lymphocyte Count
Mucins
Bronchi
Mucus
Interleukin-10
Allergens
Coloring Agents

Keywords

  • 1L-4 expression
  • Airway epithelium
  • Mucin production
  • Ovalbumin sensitization

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Suplatast tosilate inhibits goblet-cell metaplasia of airway epithelium in sensitized mice. / Shim, Jae Jeong; Dabbagh, Karim; Takeyama, Kiyoshi; Burgel, Pierre Regis; Dao-Pick, Trang P.; Ueki, Iris F.; Nadel, Jay A.

In: Journal of Allergy and Clinical Immunology, Vol. 105, No. 4, 01.01.2000, p. 739-745.

Research output: Contribution to journalArticle

Shim, Jae Jeong ; Dabbagh, Karim ; Takeyama, Kiyoshi ; Burgel, Pierre Regis ; Dao-Pick, Trang P. ; Ueki, Iris F. ; Nadel, Jay A. / Suplatast tosilate inhibits goblet-cell metaplasia of airway epithelium in sensitized mice. In: Journal of Allergy and Clinical Immunology. 2000 ; Vol. 105, No. 4. pp. 739-745.
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abstract = "Background: IL-4 and IL-13 play a putative role in mucus hypersecretion in asthma. Suplatast tosilate prevents the synthesis of T(H2) cytokines. Objective: Because suplatast tosilate inhibits T(H2) cytokines but does not inhibits IFN-γ production, we examined the effect of suplatast on IL-4- or IL-13- and ovalbumin (OVA)-induced mucin synthesis in NCI-H292 cells in vitro and in bronchi of pathogen-free BALB/c mice in vivo. Methods: In vitro, NCI- H292 cells were preincubated with suplatast tosilate (0.1-100 μg/mL) 1 hour before adding human recombinant IL-4 (10 ng/mL). In vivo, mouse recombinant IL-4 or IL-13 (250 ng per/mouse) was instilled intranasally in mice pretreated with suplatast tosilate (50 mg · kg-1 · d-1). Mucous glycoconjugates were stained with Alcian blue (AB)/periodic acid-Schiff (PAS) stain. To evaluate effects of suplatast tosilate on goblet-cell metaplasia in OVA-sensitized mice, animals were pretreated with suplatast tosilate (1-50 mg · kg-1 · d-1) intragastrically. IL-4 and IL-13 were measured, and allergic inflammatory cells were analyzed in bronchoalveolar lavage fluid of OVA-sensitized mice. Results: Pretreatment with suplastast did not prevent IL-4- or IL-13-induced increase in mucous glycoconjugate production in NCI- H292 cells or in mice. OVA sensitization increased AB/PAS-stained area of the epithelium (48.1{\%} ± 2.4{\%}, P < .01 compared with control mice). Suplatast tosilate inhibited OVA-induced goblet-cell metaplasia in airway epithelium in a dose-dependent fashion; 50 mg · kg-1 · d-1 decreased the AB/PAS area to 22.7{\%} ± 2.7{\%} (P < .05 compared with OVA sensitization alone). Pre- treatment with suplatast tosilate also prevented OVA-induced increase in IL-4 and IL-13 levels and decreased the number of lymphocytes and eosinophils in bronchoalveolar lavage fluid (P < .05 compared with values of mice given OVA alone). Conclusion: These results indicate that suplatast tosilate prevents allergen-induced goblet-cell metaplasia and the recruitment of eosinophils and lymphocytes into the airways. These results suggest that this effect is due to the prevention of the production of T(H2) cytokines in airways.",
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T1 - Suplatast tosilate inhibits goblet-cell metaplasia of airway epithelium in sensitized mice

AU - Shim, Jae Jeong

AU - Dabbagh, Karim

AU - Takeyama, Kiyoshi

AU - Burgel, Pierre Regis

AU - Dao-Pick, Trang P.

AU - Ueki, Iris F.

AU - Nadel, Jay A.

PY - 2000/1/1

Y1 - 2000/1/1

N2 - Background: IL-4 and IL-13 play a putative role in mucus hypersecretion in asthma. Suplatast tosilate prevents the synthesis of T(H2) cytokines. Objective: Because suplatast tosilate inhibits T(H2) cytokines but does not inhibits IFN-γ production, we examined the effect of suplatast on IL-4- or IL-13- and ovalbumin (OVA)-induced mucin synthesis in NCI-H292 cells in vitro and in bronchi of pathogen-free BALB/c mice in vivo. Methods: In vitro, NCI- H292 cells were preincubated with suplatast tosilate (0.1-100 μg/mL) 1 hour before adding human recombinant IL-4 (10 ng/mL). In vivo, mouse recombinant IL-4 or IL-13 (250 ng per/mouse) was instilled intranasally in mice pretreated with suplatast tosilate (50 mg · kg-1 · d-1). Mucous glycoconjugates were stained with Alcian blue (AB)/periodic acid-Schiff (PAS) stain. To evaluate effects of suplatast tosilate on goblet-cell metaplasia in OVA-sensitized mice, animals were pretreated with suplatast tosilate (1-50 mg · kg-1 · d-1) intragastrically. IL-4 and IL-13 were measured, and allergic inflammatory cells were analyzed in bronchoalveolar lavage fluid of OVA-sensitized mice. Results: Pretreatment with suplastast did not prevent IL-4- or IL-13-induced increase in mucous glycoconjugate production in NCI- H292 cells or in mice. OVA sensitization increased AB/PAS-stained area of the epithelium (48.1% ± 2.4%, P < .01 compared with control mice). Suplatast tosilate inhibited OVA-induced goblet-cell metaplasia in airway epithelium in a dose-dependent fashion; 50 mg · kg-1 · d-1 decreased the AB/PAS area to 22.7% ± 2.7% (P < .05 compared with OVA sensitization alone). Pre- treatment with suplatast tosilate also prevented OVA-induced increase in IL-4 and IL-13 levels and decreased the number of lymphocytes and eosinophils in bronchoalveolar lavage fluid (P < .05 compared with values of mice given OVA alone). Conclusion: These results indicate that suplatast tosilate prevents allergen-induced goblet-cell metaplasia and the recruitment of eosinophils and lymphocytes into the airways. These results suggest that this effect is due to the prevention of the production of T(H2) cytokines in airways.

AB - Background: IL-4 and IL-13 play a putative role in mucus hypersecretion in asthma. Suplatast tosilate prevents the synthesis of T(H2) cytokines. Objective: Because suplatast tosilate inhibits T(H2) cytokines but does not inhibits IFN-γ production, we examined the effect of suplatast on IL-4- or IL-13- and ovalbumin (OVA)-induced mucin synthesis in NCI-H292 cells in vitro and in bronchi of pathogen-free BALB/c mice in vivo. Methods: In vitro, NCI- H292 cells were preincubated with suplatast tosilate (0.1-100 μg/mL) 1 hour before adding human recombinant IL-4 (10 ng/mL). In vivo, mouse recombinant IL-4 or IL-13 (250 ng per/mouse) was instilled intranasally in mice pretreated with suplatast tosilate (50 mg · kg-1 · d-1). Mucous glycoconjugates were stained with Alcian blue (AB)/periodic acid-Schiff (PAS) stain. To evaluate effects of suplatast tosilate on goblet-cell metaplasia in OVA-sensitized mice, animals were pretreated with suplatast tosilate (1-50 mg · kg-1 · d-1) intragastrically. IL-4 and IL-13 were measured, and allergic inflammatory cells were analyzed in bronchoalveolar lavage fluid of OVA-sensitized mice. Results: Pretreatment with suplastast did not prevent IL-4- or IL-13-induced increase in mucous glycoconjugate production in NCI- H292 cells or in mice. OVA sensitization increased AB/PAS-stained area of the epithelium (48.1% ± 2.4%, P < .01 compared with control mice). Suplatast tosilate inhibited OVA-induced goblet-cell metaplasia in airway epithelium in a dose-dependent fashion; 50 mg · kg-1 · d-1 decreased the AB/PAS area to 22.7% ± 2.7% (P < .05 compared with OVA sensitization alone). Pre- treatment with suplatast tosilate also prevented OVA-induced increase in IL-4 and IL-13 levels and decreased the number of lymphocytes and eosinophils in bronchoalveolar lavage fluid (P < .05 compared with values of mice given OVA alone). Conclusion: These results indicate that suplatast tosilate prevents allergen-induced goblet-cell metaplasia and the recruitment of eosinophils and lymphocytes into the airways. These results suggest that this effect is due to the prevention of the production of T(H2) cytokines in airways.

KW - 1L-4 expression

KW - Airway epithelium

KW - Mucin production

KW - Ovalbumin sensitization

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DO - 10.1067/mai.2000.105221

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