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Theophylline induces apoptosis of the IL-3 activated eosinophils of patients with bronchial asthma

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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.

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Authors and Affiliations

  1. Second Department of Internal Medicine, Nagoya University School of Medicine, Nagoya, Japan

    M. Takeuchi, K. Hiramatsu, Y. Shimizu, Y. Ito, H. Kume & K. Yamaki

  2. Equipment Center for Research and Education, Japan

    A. Hayakawa

  3. Department of Medical Technology, Nagoya University Schoolof Health Sciences, 1-1-20 Daikominami, Higashi-ku, Nagoya, 461-8673, Japan

    K. Takagi

  4. Department of Respiratory Medicine, Komaki Municipal Hospital, Komaki, Japan

    S. Matsumoto & T. Hiramatsu

  5. Department of Laboratory Medicine, Department of Medical Technology, Nagoya University School of Health Sciences, 1-1-20 Daikominami, Higashi-ku, Nagoya, 461-8673, Japan

    R. Suzuki

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  1. M. Takeuchi
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  2. A. Hayakawa
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  3. K. Takagi
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  4. K. Hiramatsu
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  5. Y. Shimizu
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  6. S. Matsumoto
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  7. T. Hiramatsu
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  8. Y. Ito
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  9. H. Kume
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  10. R. Suzuki
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  11. K. Yamaki
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Takeuchi, M., Hayakawa, A., Takagi, K. et al. Theophylline induces apoptosis of the IL-3 activated eosinophils of patients with bronchial asthma. Apoptosis 4, 461–468 (1999). https://doi.org/10.1023/A:1009656527168

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