Selective phosphodiesterase type 4 inhibitors reduce the prolonged survival of eosinophils stimulated by granulocyte-macrophage colony-stimulating factor.
It is well known that bronchial asthma is defined as chronic eosinophilic inflammation of the respiratory tract and that as one of the various types of inflammatory cells, eosinophils induce the airway inflammation of chronic asthma. Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been shown to play an important role in the prolongation of the survival of eosinophils. We investigated the inhibitory effect of the selective phosphodiesterase (PDE) 4 inhibitors, 3,4-dipropyl-4,5,7,8-tetrahydro-3H-imidazo[1,2-i]purin-5-one (XT-611) and rolipram, and the nonselective PDE inhibitor theophylline, against GM-CSF-induced prolongation of the survival of eosinophils isolated from patients with bronchial asthma. Eosinophils (10(6) cells/ml) were incubated in the presence of GM-CSF together with or without theophylline, rolipram or XT-611 at 37 degrees C, and the viable cells were assessed up to 4d using Trypan blue dye exclusion. The presence of theophylline (10(-4) M), rolipram (10(-4)-10(-5) M) or XT-611 (10(-4)-10(-5) M) significantly reduced the GM-CSF (10 pg/ml)-induced prolongation of viability of eosinophils. These findings suggest that selective PDE 4 inhibitors, including XT-611, may effectively reduce the activities of inflammatory cells in the airway of bronchial asthma patients.
Takeuchi
Masayuki
M
Second Department of Internal Medicine and Laboratory Medicine, Nagoya University School of Medicine, Japan.
Tatsumi
Yasuaki
Y
Kitaichi
Kiyoyuki
K
Baba
Kenji
K
Suzuki
Ryujiro
R
Shibata
Eiji
E
Takagi
Kenji
K
Miyamoto
Ken-ichi
K
Hasegawa
Takaaki
T
Takagi
Kenzo
K
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D004804:Eosinophils / Q000187:drug effects* / Q000502:physiology; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D008297:Male; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D011687:Purines / Q000494:pharmacology*; D020889:Rolipram / Q000494:pharmacology; D013806:Theophylline / Q000494:pharmacology
C461440:3,4-dipropyl-4,5,7,8-tetrahydro-3H-imidazo(1,2-i)purin-5-one; D010726:Phosphodiesterase Inhibitors; D011687:Purines; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D013806:Theophylline; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D020889:Rolipram