title: Theophylline induces apoptosis of the IL-3 activated eosinophils of patients with bronchial asthma.
abstract: In bronchial asthma, eosinophils are upregulated and their survival is suggested to be prolonged by the action of some cytokines such as Interleukin (IL)-3, IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF). We find here that the survival of eosinophils in the peripheral blood of patients with asthma is correlated with the serum levels of IL-3 but not of IL-5 and GM-CSF. Interestingly, theophylline is revealed to induce apoptosis of the prolonged survival eosinophils by IL-3, as judged by morphological changes and nucleosomal DNA fragmentation. During the apoptosis, caspase-3 in eosinophils stimulated by IL-3 is activated by theophylline. The substrate of caspase-3, poly (ADP-ribose) polymerase (PARP), is cleaved in the eosinophils after theophylline treatment. These results suggest that theophylline is able to induce apoptosis of the IL-3 activated eosinophils in patients with bronchial asthma, and that its clinical effectiveness may be due to the reduction of inflammatory cells in the airway.
authors.affiliation: Second Department of Internal Medicine, Nagoya University School of Medicine, Nagoya, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Takeuchi
authors.forename: A
authors.initials: A
authors.lastname: Hayakawa
authors.forename: K
authors.initials: K
authors.lastname: Takagi
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authors.initials: K
authors.lastname: Hiramatsu
authors.forename: Y
authors.initials: Y
authors.lastname: Shimizu
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authors.initials: S
authors.lastname: Matsumoto
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authors.initials: T
authors.lastname: Hiramatsu
authors.forename: Y
authors.initials: Y
authors.lastname: Ito
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authors.initials: H
authors.lastname: Kume
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authors.initials: R
authors.lastname: Suzuki
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authors.initials: K
authors.lastname: Yamaki