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 language | English |
|---|---|
| Pages (from-to) | 103-108 |
| Number of pages | 6 |
| Journal | Biochemical and Biophysical Research Communications |
| Volume | 390 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Dec 4 2009 |
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All Science Journal Classification (ASJC) codes
- Biophysics
- Biochemistry
- Molecular Biology
- Cell Biology
Cite this
Demethylallosamidin, a chitinase inhibitor, suppresses airway inflammation and hyperresponsiveness. / Matsumoto, Takafumi; Inoue, Hiromasa; Sato, Yosuke; Kita, Yoshihiro; Nakano, Takako; Noda, Naotaka; Eguchi-Tsuda, Miyuki; Moriwaki, Atsushi; Kan-o, Keiko; Matsumoto, Koichiro; Shimizu, Takao; Nagasawa, Hiromichi; Sakuda, Shohei; Nakanishi, Yoichi.
In: Biochemical and Biophysical Research Communications, Vol. 390, No. 1, 04.12.2009, p. 103-108.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Demethylallosamidin, a chitinase inhibitor, suppresses airway inflammation and hyperresponsiveness
AU - Matsumoto, Takafumi
AU - Inoue, Hiromasa
AU - Sato, Yosuke
AU - Kita, Yoshihiro
AU - Nakano, Takako
AU - Noda, Naotaka
AU - Eguchi-Tsuda, Miyuki
AU - Moriwaki, Atsushi
AU - Kan-o, Keiko
AU - Matsumoto, Koichiro
AU - Shimizu, Takao
AU - Nagasawa, Hiromichi
AU - Sakuda, Shohei
AU - Nakanishi, Yoichi
PY - 2009/12/4
Y1 - 2009/12/4
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=70349964407&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=70349964407&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2009.09.075
DO - 10.1016/j.bbrc.2009.09.075
M3 - Article
C2 - 19782048
AN - SCOPUS:70349964407
VL - 390
SP - 103
EP - 108
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 1
ER -