Acetamide-45 inhibited hyperresponsiveness and airway inflammation in mice partly depending on phosphodiesterase activity suppression.
OBJECTIVE
Asthma is characterized as a chronic inflammatory disorder of the airways. Phosphodiesterases (PDE), which hydrolyze cAMP, are considered to play important roles in asthma. We previously reported that acetamide-45 could inhibit cAMP-PDE activity, and histamine- and methacholine-induced contractions of isolated guinea pig trachea. The purpose of this study is to determine whether this agent could suppress allergic-induced airway hyperresponsiveness (AHR) and airway inflammation in allergic mice.


METHODS
A mouse model for asthma was used to investigate acetamide-45 on the airway lesions compared with glucocorticoids. The study was conducted on mice sensitized and challenged with ovalbumin and the whole body plethysmography was carried out to assess AHR. The bronchoalveolar lavage (BAL) histopathology was examined.


RESULTS
We found that acetamide-45 significantly inhibited the enhanced hyperresponsiveness and eosinophil recruitment in airways with elimination of cAMP-PDE activity in lung tissue. Elevated IL-4 and IL-5 in bronchoalveolar lavage fluid (BALF) in asthmatic mice were markedly decreased.


CONCLUSIONS
Our results indicate that the agent has a potential role in inflammatory disease.
Wang
Kai
K
Department of Respiratory Medicine, Second Affiliated Hospital, Medical School of Zhejiang University, Hangzhou 310009, China.
Shen
Hua-hao
HH
Huang
Hua-qiong
HQ
Chen
Jun-chun
JC
Chen
Zhong
Z
D000081:Acetamides / Q000494:pharmacology*; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000188:drug therapy*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D004804:Eosinophils / Q000187:drug effects; D006967:Hypersensitivity / Q000473:pathology; D007211:Indoles / Q000494:pharmacology*; D007249:Inflammation / Q000378:metabolism*; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D015848:Interleukin-5 / Q000378:metabolism; D007962:Leukocytes / Q000187:drug effects; D008168:Lung / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*
D000081:Acetamides; D007211:Indoles; D015848:Interleukin-5; D010726:Phosphodiesterase Inhibitors; C522433:acetamide 45; D015847:Interleukin-4; D007371:Interferon-gamma; D010047:Ovalbumin