title: Phosphodiesterases inhibition by Bacilli Calmette-Guérin contributes to decrease asthma in allergic rats.
abstract: Phosphodiesterases (PDE) hydrolyse intracellular cAMP and cGMP to inactive 5' monophosphates. Decreased level of cAMP is involved in the pathogenesis of asthma. We and others have shown that phosphodiesterases were upregulated in the lung of allergic rats, and Bacilli Calmette-Guérin (BCG) induced the production of cAMP in vitro. However, it is unclear how BCG's effect asthma and whether it is related to PDEs.In this study, BCG was intraperitoneally injected into male Sprague-Dawley rats sensitized and later the rats were challenged with ovabumin/pertusis. The inflammation in lungs was measured. Airway hyperresponsiveness was determined using MedLab software after intravenous methacholine challenge. Furthermore, cAMP level and adenylate cyclase activity in lungs were analyzed by ELISA, phosphodiesterases activities were analyzed by HPLC, while PDEs mRNA levels in lungs was analyzed by reverse transcription-polymerase chain reaction. Administration of BCG significantly attenuated allergen-induced lung inflammatory response and hyper responsiveness as compared with vehicle treatment. Furthermore, the levels of cAMP in lungs were significantly increased in BCG-treated allergic rats. Interestingly, administration of BCG decreased the activity of cAMP-PDE, but not adenylyl cyclase (AC), activity in lungs of animals. Furthermore, pretreatment with BCG significantly decreased the mRNA levels of PDE4A, 4C, 5 and 8, which were induced in lungs of allergic rats. BCG administration attenuated airway inflammatory response and bronchial hyper responsiveness in rats, which are the most important symptoms in asthma. The decreased PDEs mRNA and inhibited cAMP-PDE activities by BCG contribute, at least in part, prevention of allergen-induced airway inflammation and asthma in rats.
authors: Zhejiang Respiratory Drugs Research Laboratory of State Food and Drug Administration of China, College of Medicine, Zhejiang University, Hangzhou 310058, China.
authors: Yajuan
authors: Y
authors: Wang
authors: Yali
authors: Y
authors: Jiang
authors: Huifang
authors: H
authors: Tang
authors: Xuefeng
authors: X
authors: Wang
authors: Chunzhen
authors: C
authors: Zhao
authors: Jiqiang
authors: J
authors: Chen
mesh_terms: D000818:Animals; D001249:Asthma / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D001500:BCG Vaccine / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D006967:Hypersensitivity / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D008297:Male; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism*; D011014:Pneumonia / Q000201:enzymology / Q000276:immunology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D001500:BCG Vaccine; D010726:Phosphodiesterase Inhibitors; D010727:Phosphoric Diester Hydrolases