The downregulation of Bcl-2 expression is necessary for theophylline-induced apoptosis of eosinophil.
Apoptosis of eosinophils is of increasingly important value in modulating allergic inflammatory airway diseases, such as asthma, and is suppressed by interleukin-5 (IL-5) in in vitro culture. In this study, we examined the effects of theophylline on survival/apoptosis, intracellular cAMP concentration, and Bcl-2 protein expression. Treatment with theophylline protected eosinophils against IL-5-mediated inhibition of apoptosis with a simultaneous suppression of survival in a dose-dependent manner. Theophylline caused an increase in the intracellular cAMP levels of IL-5-stimulated eosinophils. Enhancement of eosinophil apoptosis was consistent with an increase in DNA fragmentation in eosinophils treated with theophylline. On the other hand, the Bcl-2 protein appeared to be expressed constitutively in freshly isolated eosinophils. Bcl-2 expression was augmented by IL-5 stimulation, yet it was considerably inhibited by theophylline treatment. These data suggest that intracellular cAMP levels and Bcl-2 expression are involved in the suppression of eosinophil survival by theophylline.
Chung
I Y
IY
Division of Allergy and Respiratory Medicine, Soonchunhyang University Hospital, Seoul, Korea.
Nam-Kung
E K
EK
Lee
N M
NM
Chang
H S
HS
Kim
D J
DJ
Kim
Y H
YH
Park
C S
CS
D012368:4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D015536:Down-Regulation; D004804:Eosinophils / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D015848:Interleukin-5 / Q000494:pharmacology; D007424:Intracellular Fluid / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000378:metabolism* / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis*; D013806:Theophylline / Q000378:metabolism* / Q000494:pharmacology
D015848:Interleukin-5; D010726:Phosphodiesterase Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D012368:4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone; D013806:Theophylline; D000242:Cyclic AMP; D007545:Isoproterenol