Demethylallosamidin, a chitinase inhibitor, suppresses airway inflammation and hyperresponsiveness.
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 PGE(2) levels in BAL fluids were elevated after IL-13 instillation. Allo, but not Dma, suppressed the overproduction of PGE(2) 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 PGE(2) synthesis. Dma may have potential as therapeutic agents for asthma.
Matsumoto
Takafumi
T
Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Inoue
Hiromasa
H
Sato
Yosuke
Y
Kita
Yoshihiro
Y
Nakano
Takako
T
Noda
Naotaka
N
Eguchi-Tsuda
Miyuki
M
Moriwaki
Atsushi
A
Kan-O
Keiko
K
Matsumoto
Koichiro
K
Shimizu
Takao
T
Nagasawa
Hiromichi
H
Sakuda
Shohei
S
Nakanishi
Yoichi
Y
D000117:Acetylglucosamine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000485:Allergens / Q000276:immunology; D000818:Animals; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D054413:Chemokine CCL11 / Q000096:biosynthesis; D002688:Chitinases / Q000037:antagonists & inhibitors*; D052246:Cyclooxygenase 2 Inhibitors / Q000627:therapeutic use; D015536:Down-Regulation; D018793:Interleukin-13 / Q000494:pharmacology; D008168:Lung / Q000187:drug effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D011014:Pneumonia / Q000188:drug therapy* / Q000276:immunology; D014312:Trisaccharides / Q000627:therapeutic use*
D000485:Allergens; D054413:Chemokine CCL11; D052246:Cyclooxygenase 2 Inhibitors; D018793:Interleukin-13; D014312:Trisaccharides; C054851:allosamidin; C070537:methyl-N-demethylallosamidin; D010047:Ovalbumin; D002688:Chitinases; D000117:Acetylglucosamine