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Suplatast tosilate inhibits goblet-cell metaplasia of airway epithelium in sensitized mice  Jae Jeong Shim, MD, Karim Dabbagh, PhD, Kiyoshi Takeyama, MD,

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Presentation on theme: "Suplatast tosilate inhibits goblet-cell metaplasia of airway epithelium in sensitized mice  Jae Jeong Shim, MD, Karim Dabbagh, PhD, Kiyoshi Takeyama, MD,"— Presentation transcript:

1 Suplatast tosilate inhibits goblet-cell metaplasia of airway epithelium in sensitized mice 
Jae Jeong Shim, MD, Karim Dabbagh, PhD, Kiyoshi Takeyama, MD, Pierre-Regis Burgel, MD, Trang P. Dao-Pick, BA, Iris F. Ueki, BA, Jay A. Nadel, MD  Journal of Allergy and Clinical Immunology  Volume 105, Issue 4, Pages (April 2000) DOI: /mai Copyright © 2000 Mosby, Inc. Terms and Conditions

2 Fig. 1 Schematic diagram of the mechanisms of action of suplatast tosilate. APC, Antigen-presenting cell; MC, mast cell; EO, eosinophil; X, inhibitory sites of action of suplatast tosilate. Journal of Allergy and Clinical Immunology  , DOI: ( /mai ) Copyright © 2000 Mosby, Inc. Terms and Conditions

3 Fig. 2 Effect of suplatast tosilate on IL-4–induced mucous glycoconjugate production evaluated by densitometric analysis of PAS-positive material in NCI-H292 cells. Cells were treated with suplatast tosilate (0.1, 1, 10, and 100 μg/mL) 1 hour before supplementation with human recombinant IL-4 (10 ng/mL) for 24 hours. Values are expressed as means ± SEM of 3 separate experiments (n = 5; *P < .05 compared with control medium). Journal of Allergy and Clinical Immunology  , DOI: ( /mai ) Copyright © 2000 Mosby, Inc. Terms and Conditions

4 Fig. 3 Photomicrographs of the effect of suplatast tosilate on AB/PAS staining induced by instillation of IL-4 in bronchial epithelium in mice. A, In control animals AB/PAS staining was absent or minimal. B, Instillation of IL-4 (250 ng per mouse intranasally instilled twice at 24-hour intervals) increased AB/PAS staining. C, Pretreatment with suplatast tosilate (50 mg/kg intragastrically given 6 hours before intranasal instillation of IL-4 and daily thereafter) did not inhibit IL-4–induced AB/PAS staining. Photomicrographs are shown at 10× magnification; inserts show magnification at 40× (bars = 100 μm). Journal of Allergy and Clinical Immunology  , DOI: ( /mai ) Copyright © 2000 Mosby, Inc. Terms and Conditions

5 Fig. 4 Effect of suplatast tosilate on percentage area of bronchial epithelium stained positively with AB/PAS in mice given IL-4 or IL-13 by means of instillation. Instillation of IL-4 or IL-13 (250 ng per mouse administered intranasally instilled twice at 24-hour intervals) increased AB/PAS-positive staining, but pretreatment with suplatast tosilate (50 mg/kg intragastrically given 6 hours before intranasal instillation of IL-4 or IL-13 and daily thereafter) did not inhibit IL-4– or IL-13–induced AB/PAS-positive staining. Values are expressed as means ± SEM (n = 5; *P < .01 compared with mice given PBS alone; †P > .05 compared with mice given the cytokine alone). Journal of Allergy and Clinical Immunology  , DOI: ( /mai ) Copyright © 2000 Mosby, Inc. Terms and Conditions

6 Fig. 5 Photomicrographs of the effect of suplatast tosilate on AB/PAS staining in bronchial epithelium in mice sensitized to OVA. A , In control animals AB/PAS staining was absent or minimal. B , OVA sensitization increased AB/PAS staining markedly. C , Pretreatment with suplatast tosilate (50 mg · kg–1 · d–1) intragastrically given for the duration of the experiment had an inhibitory effect on the OVA-induced increase in AB/PAS staining. Photomicrographs are shown at ×10 magnification; inserts show magnification at ×40 (bars = 100 μm). Journal of Allergy and Clinical Immunology  , DOI: ( /mai ) Copyright © 2000 Mosby, Inc. Terms and Conditions

7 Fig. 6 Effect of suplatast tosilate on percentage area of bronchial epithelium stained positively with AB/PAS in mice sensitized to OVA. Instillation of OVA in sensitized mice increased AB/PAS-positive staining. Pretreatment with suplatast tosilate (1 to 50 mg·kg–1·d–1) intragastrically given for the duration of the experiment inhibited the OVA-induced increase in AB/PAS-positive staining in a dose-dependent fashion. Values are expressed as means ± SEM (n = 5; *P < .01 compared with mice given PBS alone [control]; †P < .05 compared with mice given OVA alone). Journal of Allergy and Clinical Immunology  , DOI: ( /mai ) Copyright © 2000 Mosby, Inc. Terms and Conditions

8 Fig. 7 Effect of suplatast tosilate on levels of IL-4 and IL-13 in BAL fluid 6 and 24 hours after OVA challenge in sensitized mice. In control mice IL-4 and IL-13 were not measurable. Lavage 6 hours after OVA challenge showed increased levels of both IL-4 and IL-13, and the levels at 24 hours were increased further (solid columns) . IL-4 levels were greater than levels of IL-13. Pretreatment with suplatast tosilate for the duration of the experiment (hatched columns) inhibited the production of the cytokines. Values are expressed as means ± SEM (n = 5; *P < .05 compared with mice given OVA alone). Journal of Allergy and Clinical Immunology  , DOI: ( /mai ) Copyright © 2000 Mosby, Inc. Terms and Conditions

9 Fig. 8 Effect of suplatast tosilate on cell analysis of BAL fluid 24 hours after OVA challenge in sensitized mice. Numbers of all cells in BAL fluid were significantly greater for OVA-challenged mice (solid columns) than for control mice (open columns) . Pretreatment with suplatast tosilate for the duration of the experiment (hatched columns) inhibited recruitment of eosinophils and lymphocytes in BAL fluid. Values are expressed as means ± SEM (n = 5; *P < .01 compared with mice given PBS alone; †P < .05 compared with mice given OVA alone). Journal of Allergy and Clinical Immunology  , DOI: ( /mai ) Copyright © 2000 Mosby, Inc. Terms and Conditions

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