|
|||||
|
|
Demethylallosamidin, a chitinase inhibitor, suppresses airway inflammation and hyperresponsiveness |
|
| Authors: | Takafumi Matsumoto Yosuke Sato Takako Nakano Miyuki Eguchi-Tsuda Keiko Kan-o Takao Shimizu Shohei Sakuda Yoichi Nakanishi |
| Institution: | a Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan b Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Japan c Department of Biochemistry and Molecular Biology, Faculty of Medicine, The University of Tokyo, Tokyo, Japan |
| 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. |
| Keywords: | Asthma Chitinase inhibitor IL-13 Inflammation Lipid mediator |
| 本文献已被 ScienceDirect 等数据库收录！ | |