Effect of fudosteine, a cysteine derivative, on airway hyperresponsiveness, inflammation, and remodeling in a murine model of asthma

Tomoe Iio, Misako Shibakura, Koji Iio, Yasushi Tanimoto, Arihiko Kanehiro, Mitsune Tanimoto, Mikio Kataoka

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Aims Fudosteine is a cysteine derivative that is used as an expectorant in chronic bronchial inflammatory disorders. It has been shown to decrease the number of goblet cells in an animal model. This study examined the effects of fudosteine on airway inflammation and remodeling in a murine model of chronic asthma. Main methods BALB/c mice were sensitized by an intraperitoneal injection of ovalbumin (OVA), and subsequently challenged with nebulized ovalbumin three days a week for four weeks. Seventy-two hours after the fourth challenge, airway hyperresponsiveness (AHR) and the cell composition of bronchoalveolar lavage (BAL) fluid were assessed. Fudosteine was administered orally at 10 mg/kg or 100 mg/kg body weight from the first to the fourth challenge. Key findings We investigated the effects of fudosteine on the development of allergic airway inflammation and airway hyperresponsiveness after chronic allergen challenges. The administration of fudosteine during the challenge with ovalbumin prevented the development of airway hyperresponsiveness and accumulation of lymphocytes in the airways. Eotaxin, IL-4, and TGF-β levels and the relative intensity of matrix metalloproteinase-2 and matrix metalloproteinase-9 (MMP-2 and MMP-9) in BAL fluid were reduced by the fudosteine treatment; however, the number of eosinophils in BAL fluid and serum IgE levels did not change. The expression of TGF-β, the development of goblet cell hyperplasia, subepithelial collagenization, and basement membrane thickening were also reduced by the fudosteine treatment. Significance These results indicate that fudosteine is effective in reducing airway hyperresponsiveness, airway inflammation, and airway remodeling in a murine model of chronic asthma.

Original languageEnglish
Pages (from-to)1015-1023
Number of pages9
JournalLife Sciences
Volume92
Issue number20-21
DOIs
Publication statusPublished - May 30 2013

Fingerprint

Cysteine
Asthma
Inflammation
Derivatives
Ovalbumin
Bronchoalveolar Lavage Fluid
Airway Remodeling
Goblet Cells
Matrix Metalloproteinases
Fluids
Expectorants
fudosteine
Matrix Metalloproteinase 2
Matrix Metalloproteinase 9
Lymphocytes
Intraperitoneal Injections
Eosinophils
Basement Membrane
Interleukin-4
Allergens

Keywords

  • Airway hyperresponsiveness
  • Airway inflammation
  • Airway remodeling
  • Chronic asthma
  • Fudosteine
  • Matrix metalloproteinases

ASJC Scopus subject areas

  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Effect of fudosteine, a cysteine derivative, on airway hyperresponsiveness, inflammation, and remodeling in a murine model of asthma. / Iio, Tomoe; Shibakura, Misako; Iio, Koji; Tanimoto, Yasushi; Kanehiro, Arihiko; Tanimoto, Mitsune; Kataoka, Mikio.

In: Life Sciences, Vol. 92, No. 20-21, 30.05.2013, p. 1015-1023.

Research output: Contribution to journalArticle

Iio, Tomoe ; Shibakura, Misako ; Iio, Koji ; Tanimoto, Yasushi ; Kanehiro, Arihiko ; Tanimoto, Mitsune ; Kataoka, Mikio. / Effect of fudosteine, a cysteine derivative, on airway hyperresponsiveness, inflammation, and remodeling in a murine model of asthma. In: Life Sciences. 2013 ; Vol. 92, No. 20-21. pp. 1015-1023.
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AU - Iio, Tomoe

AU - Shibakura, Misako

AU - Iio, Koji

AU - Tanimoto, Yasushi

AU - Kanehiro, Arihiko

AU - Tanimoto, Mitsune

AU - Kataoka, Mikio

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AB - Aims Fudosteine is a cysteine derivative that is used as an expectorant in chronic bronchial inflammatory disorders. It has been shown to decrease the number of goblet cells in an animal model. This study examined the effects of fudosteine on airway inflammation and remodeling in a murine model of chronic asthma. Main methods BALB/c mice were sensitized by an intraperitoneal injection of ovalbumin (OVA), and subsequently challenged with nebulized ovalbumin three days a week for four weeks. Seventy-two hours after the fourth challenge, airway hyperresponsiveness (AHR) and the cell composition of bronchoalveolar lavage (BAL) fluid were assessed. Fudosteine was administered orally at 10 mg/kg or 100 mg/kg body weight from the first to the fourth challenge. Key findings We investigated the effects of fudosteine on the development of allergic airway inflammation and airway hyperresponsiveness after chronic allergen challenges. The administration of fudosteine during the challenge with ovalbumin prevented the development of airway hyperresponsiveness and accumulation of lymphocytes in the airways. Eotaxin, IL-4, and TGF-β levels and the relative intensity of matrix metalloproteinase-2 and matrix metalloproteinase-9 (MMP-2 and MMP-9) in BAL fluid were reduced by the fudosteine treatment; however, the number of eosinophils in BAL fluid and serum IgE levels did not change. The expression of TGF-β, the development of goblet cell hyperplasia, subepithelial collagenization, and basement membrane thickening were also reduced by the fudosteine treatment. Significance These results indicate that fudosteine is effective in reducing airway hyperresponsiveness, airway inflammation, and airway remodeling in a murine model of chronic asthma.

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KW - Airway remodeling

KW - Chronic asthma

KW - Fudosteine

KW - Matrix metalloproteinases

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