Demethylallosamidin, a chitinase inhibitor, suppresses airway inflammation and hyperresponsiveness

Takafumi Matsumoto, Hiromasa Inoue, Yosuke Sato, Yoshihiro Kita, Takako Nakano, Naotaka Noda, Miyuki Eguchi-Tsuda, Atsushi Moriwaki, Keiko Kan-o, Koichiro Matsumoto, Takao Shimizu, Hiromichi Nagasawa, Shohei Sakuda, Yoichi Nakanishi

Research output: Contribution to journalArticlepeer-review

28 Citations (Scopus)

Abstract

Acidic mammalian chitinase is upregulated in response to allergen exposure in the lung. We investigated the effects of chitinase inhibitors, allosamidin (Allo) and demethylallosamidin (Dma), on asthmatic responses. Mice were subjected to IL-13 instillation into the airways or to ovalbumin sensitization plus exposure with or without treatment of Allo or Dma. Airway hyperresponsiveness (AHR) and inflammation were evaluated. Allo and Dma attenuated airway eosinophilia and the upregulation of eotaxin after IL-13 instillation, while Dma, but not Allo, suppressed AHR in IL-13-induced asthma. Allo or Dma suppressed the elevated chitinase activity in BAL fluids after IL-13 to similar levels. The bronchoprotective PGE2 levels in BAL fluids were elevated after IL-13 instillation. Allo, but not Dma, suppressed the overproduction of PGE2 and the expression of COX-2 and PGE synthase-1 induced by IL-13. In ovalbumin-induced asthma, Dma suppressed AHR more strongly than Allo. These findings suggest that Dma attenuates asthmatic responses induced by IL-13 without affecting PGE2 synthesis. Dma may have potential as therapeutic agents for asthma.

Original languageEnglish
Pages (from-to)103-108
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume390
Issue number1
DOIs
Publication statusPublished - Dec 4 2009
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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